动脉内膜损伤后SDF-1对内皮祖细胞动员及归巢影响的研究
|
摘要
1.背景与目的:
冠心病是目前导致死亡的重要原因。经皮冠脉介入(Percutaneous coronary intervention, PCI)血运重建有效改善冠心病患者预后,成为本病的主要治疗手段之一。PCI术后血管再狭窄、血栓形成及血管痉挛是导致心脏事件的主要原因。药物洗脱支架的应用降低了PCI术后再狭窄率,却未降低血栓形成及血管痉挛的发生率。目前,PCI术后并发症的防治仍是心血管领域研究的热点之一。
PCI造成靶血管段机械损伤,内皮细胞剥脱,成为局部平滑肌细胞(Smooth muscle cells,SMC)迁移和增生的基础;药物洗脱支架释放的细胞毒药物雷帕霉素或紫杉醇,有效抑制平滑肌细胞SMC迁移和增生,诱导其凋亡。但细胞毒药物同时也抑制内皮细胞的迁移和增生,也诱导内皮细胞凋亡,对损伤血管的再内皮化(Reendothelialization)过程具有明显的抑制作用。损伤血管无内皮覆盖促进SMC迁移和增生,内皮下胶原暴露激活血液中凝血系统促进损伤血管局部形成血栓。此外,无内皮覆盖的血管生成一氧化氮(NO)和前列腺环素等血管保护性细胞因子的能力明显降低,是导致PCI术后血管再狭窄、血栓形成及血管痉挛的另一个重要原因。因此,及时再内皮化损伤血管可抑制SMC迁移和增生,阻断凝血系统的激活,恢复血管保护性细胞因子的生成,在PCI术后并发症的预防中起关键作用。
以往认为,血管损伤后内皮细胞剥脱,损伤局部边缘的内皮细胞增殖、迁移是再内皮化损伤血管的唯一内皮细胞来源。系列的研究表明,骨髓或外周血源性的内皮祖细胞(Endothelial progenitor cells,EPCs)在体内局部微环境的作用下能够分化成有功能的内皮细胞,整合到损伤血管壁的新生内皮中参与损伤血管的再内皮化。采用药物、细胞因子和激素等可显著动员骨髓源性EPCs进入外周血,起到加速损伤血管再内皮化,抑制新生内膜增生的作用。移植的EPCs可成功募集到损伤血管局部分化成内皮细胞参与并加速损伤血管的再内皮化,抑制新生内膜增生。
在EPCs介导的缺血组织血管新生的研究中发现,趋化因子基质细胞衍生因子-1(Stromal cell derived factor-1,SDF-1,又称CXCL12)参与缺血诱导的EPCs动员及参与介导EPCs在缺血组织中归巢。在Schober和Zernecke等的研究中发现,小鼠颈动脉损伤后损伤血管局部SDF-1表达明显上调,这种血管损伤后表达上调的SDF-1能够诱导骨髓Sca-1+lineage-祖细胞动员到外周血,并能够介导自体动员的或移植的Sca-1+lineage-祖细胞募集到血管损伤处分化成SMC参与新生内膜形成。然而,这种血管损伤后表达上调的SDF-1是否也能够诱导EPCs动员到外周血,是否也能够介导EPCs募集到血管损伤处分化成内皮细胞参与损伤血管的再内皮化,目前还未见相关报道。
为此,本研究在体外实验部分观察SDF-1对体外扩增的EPCs增殖、迁移及凋亡的影响;在动物实验部分观察小鼠颈动脉损伤后损伤血管局部SDF-1的表达变化,外周血及骨髓中SDF-1的浓度变化,同时观察血管损伤后外周血EPCs数量的改变;在动物实验部分还观察小鼠颈动脉损伤后损伤血管局部表达上调的SDF-1是否参与介导荧光标记的EPCs募集到血管损伤处,分化成内皮细胞参与损伤血管的再内皮化,抑制新生内膜的增生。
2.方法
本课题第一部分采用内皮细胞选择性培养基培养和诱导分化密度梯度离心法获得的小鼠骨髓源性单个核细胞,以获得小鼠骨髓源性EPCs,并通过acLDL-DiI和FITC-lectin荧光双染鉴定、流式细胞仪检测细胞表面干细胞抗原及内皮细胞特异性抗原鉴定和免疫组化法鉴定细胞表面内皮细胞特异性抗原的表达。小鼠骨髓源性EPCs经各种浓度的SDF-1α处理,采用acLDL-DiI和FITC-lectin荧光双阳性细胞计数、MTT分析、黏附细胞计数、TUNEL法染色及改良的Boyden小室分析来分别检测SDF-1α对EPCs数量、增殖及黏附能力和抗凋亡能力的影响,及检测SDF-1α对EPCs的诱导迁移能力。
本课题第二部分采用非显微外科手术方法建立小鼠颈动脉损伤模型,并应用扫描电镜及病理学方法检测小鼠颈动脉损伤模型是否建立成功。在小鼠颈动脉损伤后各时间点(0天、1天、3天、7天和14天)获取损伤侧颈总动脉,采用RT-PCR和Western blot检测损伤动脉SDF-1αmRNA表达及SDF-1α蛋白表达;在小鼠颈动脉损伤后各时间点(0天、1天、3天、7天和14天)获取小鼠外周血和骨髓,采用ELISA测定外周血和骨髓SDF-1α浓度,采用流式细胞仪检测外周血EPCs数量。采用抗SDF-1α单克隆抗体或IgG1同型对照注射颈动脉损伤小鼠,流式细胞仪检测动脉损伤后各时间点(0天、1天、3天、7天和14天)外周血EPCs数量,14天后通过Evans blue染色检测损伤动脉再内皮化情况及通过病理学方法检测损伤动脉内膜增生情况。
本课题第三部分采用改良的Boyden小室分析检测AMD3100(CXCR4的特异性阻断剂)对SDF-1α诱导EPCs迁移的阻断作用。采用acLDL-DiI标记的EPCs移植、CXCR4阻断的EPCs移植及无菌生理盐水注射颈动脉损伤小鼠,14天后取小鼠损伤颈动脉,纵形剖开后荧光显微镜下观察并计数acLDL-DiI阳性的EPCs在损伤动脉壁的归巢情况;采用活体注射FITC-lectin后获取小鼠损伤颈动脉,冰冻切片荧光显微镜下观察移植的细胞参与损伤动脉再内皮化情况;采用活体注射Evans blue后获取小鼠损伤颈动脉,显微镜下观察细胞移植对损伤动脉再内皮化面积的影响;通过病理学方法检测细胞移植对损伤动脉新生内膜增生的影响。
3.结果
第一部分:培养7天的小鼠骨髓单个核细胞呈梭形或纺锤状,与内皮细胞形态相似,绝大多数细胞可摄取acLDL-DiI和与lectin结合,流式细胞仪检测显示这些细胞既有干细胞抗原Sca-1的高表达,又有内皮特异性标记物VEGFR-2的高表达,免疫组化检测显示这些细胞还高表达内皮特异性标记物CD31、eNOS和vWF。荧光双染计数显示,SDF-1α刺激浓度依赖性增加小鼠骨髓单个核细胞分化成EPCs的数量;MTT分析显示,SDF-1α刺激浓度依赖性增强EPCs的增殖能力;黏附细胞计数显示,SDF-1α刺激浓度依赖性增加EPCs黏附到包被有人纤维连接蛋白的细胞培养板上的数量;TUNEL法染色显示,SDF-1α刺激浓度依赖性降低紫杉醇等诱导EPCs凋亡的数量;改良的Boyden小室分析显示,SDF-1α浓度依赖性增加迁移的EPCs数量。
第二部分:非显微外科手术方法损伤小鼠颈动脉后取损伤动脉扫描电镜下观察,损伤动脉内皮完全剥脱。RT-PCR分析显示,小鼠颈动脉损伤后1天、3天和7天,损伤血管局部SDF-1αmRNA表达明显增强,SDF-1αmRNA表达在动脉损伤后3天达到高峰;Western blot分析显示,小鼠颈动脉损伤后损伤血管局部SDF-1α蛋白合成也明显增加,与SDF-1αmRNA的表达增强一致。ELISA测定显示,小鼠颈动脉损伤后1天、3天和7天,外周血SDF-1α浓度明显高于假手术组(P<0.01),外周血SDF-1α浓度在动脉损伤后3天达到高峰;然而,骨髓SDF-1α浓度变化与外周血SDF-1α浓度变化恰好相反,小鼠颈动脉损伤后1天、3天和7天,骨髓SDF-1α浓度明显低于假手术组(P<0.01),骨髓SDF-1α浓度在动脉损伤后3天降至最低。流式细胞仪检测外周血EPCs数量显示,小鼠颈动脉损伤后1天、3天和7天,外周血EPCs数量明显高于假手术组(P<0.01),外周血EPCs数量在动脉损伤后3天达到高峰。SDF-1α单克隆抗体注射组小鼠仅动脉损伤后1天外周血EPCs数量明显高于假手术组(P<0.05),却明显低于IgG1同型对照组(P<0.05),动脉损伤后3天和7天外周血EPCs数量与假手术组无明显差异(P>0.05);Evans blue染色显示,SDF-1α单克隆抗体注射组小鼠损伤颈动脉再内皮化面积明显低于IgG1同型对照组(P<0.01),两组新生内膜面积及内膜与中膜的比值无明显差异(P>0.05)。
第三部分:改良的Boyden小室分析显示,AMD3100孵育阻断小鼠骨髓源性EPCs表面CXCR4,可有效阻断SDF-1α诱导小鼠骨髓源性EPCs迁移。细胞移植后14天,小鼠损伤颈动脉纵形剖开荧光显微镜下观察发现,EPCs移植组小鼠损伤动脉表面黏附的acLDL-DiI阳性细胞数明显多于CXCR4阻断的EPCs移植组(P<0.01);损伤颈动脉冰冻切片置荧光显微镜下观察显示,EPCs移植组许多acLDL-DiI阳性细胞覆盖在小鼠损伤颈动脉的新生内膜表面,排列成线状,这些细胞也显示具有结合lectin的能力;CXCR4阻断的EPCs移植组损伤颈动脉新生内膜表面仅覆盖少许acLDL-DiI和lectin双阳性细胞和少许lectin单阳性细胞,未形成连续的内皮细胞线;对照组损伤颈动脉新生内膜表面仅少许lectin单阳性细胞覆盖,无连续的内皮细胞线。活体Evans blue染色后取小鼠损伤颈动脉纵形剖开显微镜下观察显示,EPCs移植组小鼠损伤颈动脉再内皮化面积明显高于对照组(P<0.01)和CXCR4阻断的EPCs移植组(P<0.01);而CXCR4阻断的EPCs移植组小鼠损伤颈动脉再内皮化面积与对照组比较无明显差异(P>0.05)。小鼠损伤颈动脉病理形态学分析显示,EPCs移植组小鼠损伤颈动脉新生内膜面积明显低于对照组(P<0.01)和CXCR4阻断的EPCs移植组(P<0.01);而CXCR4阻断的EPCs移植组小鼠损伤颈动脉新生内膜面积与对照组比较无明显差异(P>0.05)。
4.结论
1. SDF-1促进骨髓干细胞分化成为EPCs,且浓度依赖性增强EPCs黏附增殖能力,有效抑制紫杉醇等诱导的EPCs凋亡,SDF-1还浓度依赖性诱导EPCs趋化迁移。
2.小鼠颈动脉损伤后损伤血管局部SDF-1表达上调,进而导致外周血SDF-1浓度升高,同时骨髓SDF-1表达下调,改变骨髓与外周血之间的SDF-1浓度剃度,从而诱导骨髓EPCs动员到外周血。阻断小鼠颈动脉损伤后SDF-1介导的EPCs动员,抑制损伤动脉的再内皮化过程。
3.动脉损伤后损伤血管局部表达上调的SDF-1与EPCs表面CXCR4的相互作用参与介导外周血EPCs归巢到损伤动脉局部分化成内皮细胞表型,促进损伤动脉再内皮化,抑制损伤动脉新生内膜增生。
4.采用内皮细胞选择性培养基培养和诱导分化密度梯度离心法获得的小鼠骨髓源性单个核细胞,可获得足量的小鼠骨髓源性EPCs供研究之用。
5.采用非显微外科手术方法可成功建立小鼠颈动脉损伤模型,其优点是无需显微外科设备、器械和专业的显微外科手术人员。
1. Background and Objective:
Revascularization procedures such as percutaneous balloon angioplasty, stent implantation, or atherectomy are widely used in the treatment of coronary artery disease but are often prone to failure because of restenosis, thrombosis, and vasospasm. Initial endothelial denudation is a major contributing factor to these consequences, in which the availability of vascular protective molecules such as nitric oxide (NO) and prostacyclin as well as antioxidant systems such as heme oxygenase-1(HO-1) are decreased, and the production of growth-promoting substances are increased, which ultimately lead to the formation of neointima. Reendothelialization at sites of spontaneous or iatrogenic endothelial denudation has classically been thought to be the result of the migration and proliferation of endothelial cells from the viable endothelium adjacent to the injury site. Neighboring endothelial cells, however, it may not constitute the exclusive source of endothelial cells for vascular repair. Recently, a series of investigations has suggested that endothelial progenitor cells (EPCs) derived from the bone marrow are present in peripheral blood and that these cells can be recruited to denuded areas and incorporated into nascent endothelium.
EPCs may be defined as adherent cells derived from peripheral blood- or bone marrow-derived mononuclear cells demonstrating ac-LDL uptake and isolectin-binding capacity. The number of circulating EPCs inversely correlates with the number of cardiovascular risk factors and is reduced in cardiovascular disease. Moreover, several studies have demonstrated that patients with coronary heart disease or severe heart failure may suffer from impaired function of peripheral circulating EPCs. EPCs mobilized or transfused systematically can home to the sites of endothelial denudation, and accelerates reendothelialization of injured arteries and effectively impairs smooth muscle cell proliferation and neointima formation. However, the means of EPCs homing to the sites of endothelial denudation is not clear yet.
First clinical trials have been performed investigating the effects of EPCs transplantation into cardiac ischemic areas after myocardial infarction, in patients with peripheral atherovascular disease, and on endothelialization of artificial heart valves. Next to EPCs transplantation, the pharmacological mobilization and functional modification of EPCs may also play a major role in future therapies.
Chemokine stromal cell derived factor-1 (SDF-1, also known as CXCL12) is constitutively produced by bone marrow stromal cells and by other cells including CD34+ cells. It was initially characterized as a pre-B cell-stimulating factor and believed to be involved in retention of hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) in bone marrow. SDF-1 has been demonstrated to increase EPCs number through enhancement of (BM) c-kit+ stem cell adhesion onto extracellular matrix components by integrin receptors and protect EPCs from serum starvation-induced apoptosis. Increasing the level of SDF-1 in perepheral blood has been shown to mobilize bone marrow-derived EPCs into peripheral blood. Up-regulated SDF-1 expression in ischemic tissues or increasing SDF-1 expression in ischemic tissues through several established methods could also mobilize bone marrow-derived EPCs into peripheral blood and mediate them home to the site of neovascularization in ischemic tissues. Recently, studies had shown that the expression of SDF-1αwas up-regulated in injured carotid arteries of apoE-/- mice, which resulted in a marked mobilization of circulating Sca-1+lineage- progenitor cells (PBPCs) in the peripheral blood and mediated these cells home to the site of neointimal lesions, where they can adopt an SMC-like phenotype. It is not clear whether the up-regulation of SDF-1αcould also induce a mobilization of EPCs and mediate them home to site of injured arteries.
In the present study, we attempted to demonstrate that SDF-1 is a biological function modificator of EPCs. For this purpose, we evaluated the effects of SDF-1 on the number, proliferation, migration, adhesiveness and apoptosis of murine bone marrow-derived EPCs. To clarify the role of local SDF-1αin repair of injured artery, we investigated the effect of up-regulated SDF-1αexpression on mobilization of EPCs in peripheral blood with fluorescence-activated cell sorter analysis after wire-induced arterial injury in mice. Furthermore, spleen-derived EPCs co-cultured with AMD3100 (a highly selective antagonist of SDF-1 that binds to its receptor, CXCR4) were injected into mice after carotid injury to evaluate the effect of local SDF-1αexpression on homing of EPCs to the site of endothelial denudation.
2. Methods:
In part one, mononuclear cells (MNCs) in murine bone marrow were isolated by density gradient centrifugation and bone marrow-derived EPCs were cultured according to previously described techniques. Murine bone marrow-derived EPCs were characterized as adherent cells double positive for DiLDL-uptake and lectin binding by direct fluorescent staining under an inverted fluorescent microscope and further documented by demonstrating the expression of Sca-1 and VEGFR-2 by flow cytometer. To investigate the potential effects of SDF-1 on EPCs biological functions, bone marrow mononuclear cells or bone marrow-derived EPCs were stimulated with different concentrations of SDF-1 (1 ng/ml,10 ng/ml or 100 ng/ml) for different times. EPCs number, proliferation, migration, adhesion and apoptosis were evaluated by counting the double positive cells, MTT assay, modified Boyden chamber assay, counting the adherent cells and TUNEL staining, respectively.
In part two, we established an injury model of the mouse carotid artery with a non- microscopical surgery method. The specimens of carotid arteries 30 minutes after the denuding procedure were examined using scanning electron microscopy, and the intimal lesion 2 weeks after injury was measured with pathological method. SDF-1αwas detected by RT-PCR and Western blot in carotid arteries of mice at different time points (day 0, day 1, day 3, day 7,day14) after wire-induced injury. Peripheral blood murine samples and bone marrow were obtained from mice at different time points after induction of vascular injury or sham operation (day 0, day 1, day 3, day 7, day 14). SDF-1 determination in peripheral blood and bone marrow samples was performed by SDF-1 enzyme-linked immunosorbent assay (ELISA) kit. EPCs were quantified in peripheral blood samples by flow cytometry. EPCs were also examined in peripheral blood samples of mice in subgroups, in which blocking SDF-1 monoclonal antibody or IgG1 isotype control was injected after vascular injury. Moreover, reendothelialization was determined by Evans blue staining in a whole vessel preparation 14 days after induction of endothelial cell damage in subgroups.
In part three, mice received either 1x106 Dil-Ac-LDL–labeled spleen-derived EPCs or 1x106 CXCR4-blocked EPCs by direct percutaneous intracardial injection after induction of arterial injury. Control animals received a corresponding amount of normal saline. Thirty minutes before euthanasia, mice received FITC-labeled lectin intravenously. A subset of these animals received an injection of Evans blue dye 10 minutes before tissue harvesting. Carotid arteries were harvested 14 days after wire injury. Some of them were sectioned for fluorescent microscopic analysis to investigate Dil-Ac-LDL positive cells and lectin expression. A subset of carotid arteries was opened longitudinally for en face microscopy to examine Dil-Ac-LDL positive cells or to measure the area of reendothelialization. H&E staining was performed for morphometric analyses, and Lucia Measurement software was used to measure external elastic lamina, internal elastic lamina, and lumen circumference as well as medial and neointimal area of carotid arteries in all sections.
3. Results:
Part one:
After 7 days in endothelial cell selection medium, bone marrow mononuclear cells turned into spindle-shaped, endothelial cell-like cells. Most of them showed uptake of ac-LDL and lectin binding, demonstrating endothelial cell characteristics. These cells were characterized further by demonstrating the expression of the mouse stem-cell marker Sca-1 as well as the endothelial cell lineage antigen VEGFR-2 by flow cytometry. Endothelial cell lineage antigen CD31, eNOS and vWF were also expressed by most of these cells in immunohistochemical analysis. Counting double fluorescent staining positive cells revealed that incubation of bone marrow mononuclear cells with SDF-1αincreased the number of differentiated, adherent EPCs in a concentration-dependent manner. Data in MTT assay showed that the proliferative activity of bone marrow-derived EPCs was improved concentration-dependently by SDF-1α. Pre-exposed to SDF-1α, the adhesive activity of EPCs was increased in a concentration-dependent manner. A dose-dependent decrease of apoptosis, which was induced by paclitaxel or serum absent media, was noticed as EPCs was incubated with SDF-1α. Data revealed that SDF-1αcould mediate obvious EPCs migration in a dose-dependent manner.
Part two:
Complete removal of the endothelium was achieved with a non-microscopical surgery method. Detected with Scanning electron microscopy, a platelet monolayer covered the denuded surface of injured carotid arteries. 2 weeks later, obvious neointimal hyperplasia was noticed in the injured carotid arteries. The results in RT-PCR and western blotting showed that up-regulation of SDF-1αmRNA and protein were already evident at 1day, and peak expression was achieved at 3 days after arterial injury. In enzyme-linked immunosorbent assay, an obvious rise in plasmatic concentration of SDF-1αwas also noticed 1 day, 3 days and 7 days after carotid injury, compared with the sham operation group (P<0.01). In contrast, a significant reduction of SDF-1αbone marrow concentration was examined 1 day, 3 days and 7 days after carotid injury, compared with the sham operation group (P<0.01). The results in fluorescence-activated cell sorting analysis showed that the amount of circulating EPCs was increased markedly 1 day, 3 days and 7 days after induction of vascular injury, compared with the sham operation group (P<0.01). In a subgroup in which blocking SDF-1αmonoclonal antibody was injected, the amount of circulating EPCs was increased lightly only at 1 day after induction of vascular injury, compared with the sham operation group (P<0.05). Interestingly, Evans blue staining showed that the reendothelialization area in the SDF-1 mAb-treated group was reduced significantly 14 days after induction of endothelial cell damage, compared with the IgG1 isotype control group (P<0.01). Surprisingly, a reduced reendothelialization in the SDF-1 mAb-treated group was not associated with an increased neointima formation, compared with the IgG1 isotype control group (P>0.05).
Part three:
In modified Boyden chamber assay, pretreatment of bone marrow-derived EPCs with 10 ng/ml AMD3100 almost completely blocked cell migration in response to 100 ng/mL SDF-1α, compared with the control (P>0.05). En face microscopy 14 days after induction of injury revealed that infusion of CXCR4-free EPCs resulted a more number of cells attached at the injury site, forming islets of transplanted cells within the deendothelialized area, compared with the group treated with CXCR4-blocked EPCs (P<0.01). Immunohistochemical analysis revealed that transfused CXCR4-free EPCs were predominantly found at the injury site, lining the intraluminal margin of the neointima. Lectin staining revealed that the attaching cells at the site of endothelial injury were lectin-positive. Overlay experiments clearly demonstrated the endothelial phenotype of transfused cells. In the CXCR4-blocked EPCs transfusion group, only few Dil-Ac-LDL- and lectin-positive cells were present, and the endothelial cell line of the neointima appeared disrupted at day 14 after induction of injury compared with the CXCR4-free EPCs treatment group. In the placebo group, a few endogenous (lectin-positive, Dil-Ac-LDL–negative) endothelial cells were present at the site of endothelial denudation, and no endothelial cell line was formed. Data in Evans blue staining revealed that transfusion of CXCR4-free EPCs was associated with a significant increase in reendothelialization area compared with the placebo group (P<0.01). But no significant increase in reendothelialization area was noted in the group of CXCR4-blocked EPCs transfusion, compared with the placebo group (P>0.05). Computer-based morphometric analysis showed that the accelerated reendothelialization after transfusion CXCR4-free EPCs was associated with a significant reduction of neointima formation compared with the placebo group (P<0.01); no change in neointima formation was detected in CXCR4-blocked EPCs treated group compared with the placebo group (P>0.05).
4. Conclusions:
1. SDF-1αcould induce EPCs migration in a dose-dependent manner, and improved the proliferative and adhesive activity of EPCs, and inhibited EPCs apoptosis in the same manner. Moreover, SDF-1αcould induce differentiation of hematopoietic stem cells toward EPCs.
2. Up-regulated SDF-1 expression after vascular injury participateded in the mobilization of EPCs through changing the gradient of SDF-1 concentration between the peripheral blood and the bone marrow. Blocking EPCs mobilization mediated by SDF-1 after vascular injury could inhibit reendothelialization of injured arteries.
3. Local SDF-1 expression in injured arteries could mediate EPCs home to the site of endothelial denudation and participate in reendothelialization of neointimal lesions.
4. Bone marrow-derived EPCs of mice can be obtained through culturing bone marrow mononuclear cells in endothelial cell selection medium.
5. Carotid artery injury model of mouse can be established by a non-microscopical surgery method.
冠心病是目前导致死亡的重要原因。经皮冠脉介入(Percutaneous coronary intervention, PCI)血运重建有效改善冠心病患者预后,成为本病的主要治疗手段之一。PCI术后血管再狭窄、血栓形成及血管痉挛是导致心脏事件的主要原因。药物洗脱支架的应用降低了PCI术后再狭窄率,却未降低血栓形成及血管痉挛的发生率。目前,PCI术后并发症的防治仍是心血管领域研究的热点之一。
PCI造成靶血管段机械损伤,内皮细胞剥脱,成为局部平滑肌细胞(Smooth muscle cells,SMC)迁移和增生的基础;药物洗脱支架释放的细胞毒药物雷帕霉素或紫杉醇,有效抑制平滑肌细胞SMC迁移和增生,诱导其凋亡。但细胞毒药物同时也抑制内皮细胞的迁移和增生,也诱导内皮细胞凋亡,对损伤血管的再内皮化(Reendothelialization)过程具有明显的抑制作用。损伤血管无内皮覆盖促进SMC迁移和增生,内皮下胶原暴露激活血液中凝血系统促进损伤血管局部形成血栓。此外,无内皮覆盖的血管生成一氧化氮(NO)和前列腺环素等血管保护性细胞因子的能力明显降低,是导致PCI术后血管再狭窄、血栓形成及血管痉挛的另一个重要原因。因此,及时再内皮化损伤血管可抑制SMC迁移和增生,阻断凝血系统的激活,恢复血管保护性细胞因子的生成,在PCI术后并发症的预防中起关键作用。
以往认为,血管损伤后内皮细胞剥脱,损伤局部边缘的内皮细胞增殖、迁移是再内皮化损伤血管的唯一内皮细胞来源。系列的研究表明,骨髓或外周血源性的内皮祖细胞(Endothelial progenitor cells,EPCs)在体内局部微环境的作用下能够分化成有功能的内皮细胞,整合到损伤血管壁的新生内皮中参与损伤血管的再内皮化。采用药物、细胞因子和激素等可显著动员骨髓源性EPCs进入外周血,起到加速损伤血管再内皮化,抑制新生内膜增生的作用。移植的EPCs可成功募集到损伤血管局部分化成内皮细胞参与并加速损伤血管的再内皮化,抑制新生内膜增生。
在EPCs介导的缺血组织血管新生的研究中发现,趋化因子基质细胞衍生因子-1(Stromal cell derived factor-1,SDF-1,又称CXCL12)参与缺血诱导的EPCs动员及参与介导EPCs在缺血组织中归巢。在Schober和Zernecke等的研究中发现,小鼠颈动脉损伤后损伤血管局部SDF-1表达明显上调,这种血管损伤后表达上调的SDF-1能够诱导骨髓Sca-1+lineage-祖细胞动员到外周血,并能够介导自体动员的或移植的Sca-1+lineage-祖细胞募集到血管损伤处分化成SMC参与新生内膜形成。然而,这种血管损伤后表达上调的SDF-1是否也能够诱导EPCs动员到外周血,是否也能够介导EPCs募集到血管损伤处分化成内皮细胞参与损伤血管的再内皮化,目前还未见相关报道。
为此,本研究在体外实验部分观察SDF-1对体外扩增的EPCs增殖、迁移及凋亡的影响;在动物实验部分观察小鼠颈动脉损伤后损伤血管局部SDF-1的表达变化,外周血及骨髓中SDF-1的浓度变化,同时观察血管损伤后外周血EPCs数量的改变;在动物实验部分还观察小鼠颈动脉损伤后损伤血管局部表达上调的SDF-1是否参与介导荧光标记的EPCs募集到血管损伤处,分化成内皮细胞参与损伤血管的再内皮化,抑制新生内膜的增生。
2.方法
本课题第一部分采用内皮细胞选择性培养基培养和诱导分化密度梯度离心法获得的小鼠骨髓源性单个核细胞,以获得小鼠骨髓源性EPCs,并通过acLDL-DiI和FITC-lectin荧光双染鉴定、流式细胞仪检测细胞表面干细胞抗原及内皮细胞特异性抗原鉴定和免疫组化法鉴定细胞表面内皮细胞特异性抗原的表达。小鼠骨髓源性EPCs经各种浓度的SDF-1α处理,采用acLDL-DiI和FITC-lectin荧光双阳性细胞计数、MTT分析、黏附细胞计数、TUNEL法染色及改良的Boyden小室分析来分别检测SDF-1α对EPCs数量、增殖及黏附能力和抗凋亡能力的影响,及检测SDF-1α对EPCs的诱导迁移能力。
本课题第二部分采用非显微外科手术方法建立小鼠颈动脉损伤模型,并应用扫描电镜及病理学方法检测小鼠颈动脉损伤模型是否建立成功。在小鼠颈动脉损伤后各时间点(0天、1天、3天、7天和14天)获取损伤侧颈总动脉,采用RT-PCR和Western blot检测损伤动脉SDF-1αmRNA表达及SDF-1α蛋白表达;在小鼠颈动脉损伤后各时间点(0天、1天、3天、7天和14天)获取小鼠外周血和骨髓,采用ELISA测定外周血和骨髓SDF-1α浓度,采用流式细胞仪检测外周血EPCs数量。采用抗SDF-1α单克隆抗体或IgG1同型对照注射颈动脉损伤小鼠,流式细胞仪检测动脉损伤后各时间点(0天、1天、3天、7天和14天)外周血EPCs数量,14天后通过Evans blue染色检测损伤动脉再内皮化情况及通过病理学方法检测损伤动脉内膜增生情况。
本课题第三部分采用改良的Boyden小室分析检测AMD3100(CXCR4的特异性阻断剂)对SDF-1α诱导EPCs迁移的阻断作用。采用acLDL-DiI标记的EPCs移植、CXCR4阻断的EPCs移植及无菌生理盐水注射颈动脉损伤小鼠,14天后取小鼠损伤颈动脉,纵形剖开后荧光显微镜下观察并计数acLDL-DiI阳性的EPCs在损伤动脉壁的归巢情况;采用活体注射FITC-lectin后获取小鼠损伤颈动脉,冰冻切片荧光显微镜下观察移植的细胞参与损伤动脉再内皮化情况;采用活体注射Evans blue后获取小鼠损伤颈动脉,显微镜下观察细胞移植对损伤动脉再内皮化面积的影响;通过病理学方法检测细胞移植对损伤动脉新生内膜增生的影响。
3.结果
第一部分:培养7天的小鼠骨髓单个核细胞呈梭形或纺锤状,与内皮细胞形态相似,绝大多数细胞可摄取acLDL-DiI和与lectin结合,流式细胞仪检测显示这些细胞既有干细胞抗原Sca-1的高表达,又有内皮特异性标记物VEGFR-2的高表达,免疫组化检测显示这些细胞还高表达内皮特异性标记物CD31、eNOS和vWF。荧光双染计数显示,SDF-1α刺激浓度依赖性增加小鼠骨髓单个核细胞分化成EPCs的数量;MTT分析显示,SDF-1α刺激浓度依赖性增强EPCs的增殖能力;黏附细胞计数显示,SDF-1α刺激浓度依赖性增加EPCs黏附到包被有人纤维连接蛋白的细胞培养板上的数量;TUNEL法染色显示,SDF-1α刺激浓度依赖性降低紫杉醇等诱导EPCs凋亡的数量;改良的Boyden小室分析显示,SDF-1α浓度依赖性增加迁移的EPCs数量。
第二部分:非显微外科手术方法损伤小鼠颈动脉后取损伤动脉扫描电镜下观察,损伤动脉内皮完全剥脱。RT-PCR分析显示,小鼠颈动脉损伤后1天、3天和7天,损伤血管局部SDF-1αmRNA表达明显增强,SDF-1αmRNA表达在动脉损伤后3天达到高峰;Western blot分析显示,小鼠颈动脉损伤后损伤血管局部SDF-1α蛋白合成也明显增加,与SDF-1αmRNA的表达增强一致。ELISA测定显示,小鼠颈动脉损伤后1天、3天和7天,外周血SDF-1α浓度明显高于假手术组(P<0.01),外周血SDF-1α浓度在动脉损伤后3天达到高峰;然而,骨髓SDF-1α浓度变化与外周血SDF-1α浓度变化恰好相反,小鼠颈动脉损伤后1天、3天和7天,骨髓SDF-1α浓度明显低于假手术组(P<0.01),骨髓SDF-1α浓度在动脉损伤后3天降至最低。流式细胞仪检测外周血EPCs数量显示,小鼠颈动脉损伤后1天、3天和7天,外周血EPCs数量明显高于假手术组(P<0.01),外周血EPCs数量在动脉损伤后3天达到高峰。SDF-1α单克隆抗体注射组小鼠仅动脉损伤后1天外周血EPCs数量明显高于假手术组(P<0.05),却明显低于IgG1同型对照组(P<0.05),动脉损伤后3天和7天外周血EPCs数量与假手术组无明显差异(P>0.05);Evans blue染色显示,SDF-1α单克隆抗体注射组小鼠损伤颈动脉再内皮化面积明显低于IgG1同型对照组(P<0.01),两组新生内膜面积及内膜与中膜的比值无明显差异(P>0.05)。
第三部分:改良的Boyden小室分析显示,AMD3100孵育阻断小鼠骨髓源性EPCs表面CXCR4,可有效阻断SDF-1α诱导小鼠骨髓源性EPCs迁移。细胞移植后14天,小鼠损伤颈动脉纵形剖开荧光显微镜下观察发现,EPCs移植组小鼠损伤动脉表面黏附的acLDL-DiI阳性细胞数明显多于CXCR4阻断的EPCs移植组(P<0.01);损伤颈动脉冰冻切片置荧光显微镜下观察显示,EPCs移植组许多acLDL-DiI阳性细胞覆盖在小鼠损伤颈动脉的新生内膜表面,排列成线状,这些细胞也显示具有结合lectin的能力;CXCR4阻断的EPCs移植组损伤颈动脉新生内膜表面仅覆盖少许acLDL-DiI和lectin双阳性细胞和少许lectin单阳性细胞,未形成连续的内皮细胞线;对照组损伤颈动脉新生内膜表面仅少许lectin单阳性细胞覆盖,无连续的内皮细胞线。活体Evans blue染色后取小鼠损伤颈动脉纵形剖开显微镜下观察显示,EPCs移植组小鼠损伤颈动脉再内皮化面积明显高于对照组(P<0.01)和CXCR4阻断的EPCs移植组(P<0.01);而CXCR4阻断的EPCs移植组小鼠损伤颈动脉再内皮化面积与对照组比较无明显差异(P>0.05)。小鼠损伤颈动脉病理形态学分析显示,EPCs移植组小鼠损伤颈动脉新生内膜面积明显低于对照组(P<0.01)和CXCR4阻断的EPCs移植组(P<0.01);而CXCR4阻断的EPCs移植组小鼠损伤颈动脉新生内膜面积与对照组比较无明显差异(P>0.05)。
4.结论
1. SDF-1促进骨髓干细胞分化成为EPCs,且浓度依赖性增强EPCs黏附增殖能力,有效抑制紫杉醇等诱导的EPCs凋亡,SDF-1还浓度依赖性诱导EPCs趋化迁移。
2.小鼠颈动脉损伤后损伤血管局部SDF-1表达上调,进而导致外周血SDF-1浓度升高,同时骨髓SDF-1表达下调,改变骨髓与外周血之间的SDF-1浓度剃度,从而诱导骨髓EPCs动员到外周血。阻断小鼠颈动脉损伤后SDF-1介导的EPCs动员,抑制损伤动脉的再内皮化过程。
3.动脉损伤后损伤血管局部表达上调的SDF-1与EPCs表面CXCR4的相互作用参与介导外周血EPCs归巢到损伤动脉局部分化成内皮细胞表型,促进损伤动脉再内皮化,抑制损伤动脉新生内膜增生。
4.采用内皮细胞选择性培养基培养和诱导分化密度梯度离心法获得的小鼠骨髓源性单个核细胞,可获得足量的小鼠骨髓源性EPCs供研究之用。
5.采用非显微外科手术方法可成功建立小鼠颈动脉损伤模型,其优点是无需显微外科设备、器械和专业的显微外科手术人员。
1. Background and Objective:
Revascularization procedures such as percutaneous balloon angioplasty, stent implantation, or atherectomy are widely used in the treatment of coronary artery disease but are often prone to failure because of restenosis, thrombosis, and vasospasm. Initial endothelial denudation is a major contributing factor to these consequences, in which the availability of vascular protective molecules such as nitric oxide (NO) and prostacyclin as well as antioxidant systems such as heme oxygenase-1(HO-1) are decreased, and the production of growth-promoting substances are increased, which ultimately lead to the formation of neointima. Reendothelialization at sites of spontaneous or iatrogenic endothelial denudation has classically been thought to be the result of the migration and proliferation of endothelial cells from the viable endothelium adjacent to the injury site. Neighboring endothelial cells, however, it may not constitute the exclusive source of endothelial cells for vascular repair. Recently, a series of investigations has suggested that endothelial progenitor cells (EPCs) derived from the bone marrow are present in peripheral blood and that these cells can be recruited to denuded areas and incorporated into nascent endothelium.
EPCs may be defined as adherent cells derived from peripheral blood- or bone marrow-derived mononuclear cells demonstrating ac-LDL uptake and isolectin-binding capacity. The number of circulating EPCs inversely correlates with the number of cardiovascular risk factors and is reduced in cardiovascular disease. Moreover, several studies have demonstrated that patients with coronary heart disease or severe heart failure may suffer from impaired function of peripheral circulating EPCs. EPCs mobilized or transfused systematically can home to the sites of endothelial denudation, and accelerates reendothelialization of injured arteries and effectively impairs smooth muscle cell proliferation and neointima formation. However, the means of EPCs homing to the sites of endothelial denudation is not clear yet.
First clinical trials have been performed investigating the effects of EPCs transplantation into cardiac ischemic areas after myocardial infarction, in patients with peripheral atherovascular disease, and on endothelialization of artificial heart valves. Next to EPCs transplantation, the pharmacological mobilization and functional modification of EPCs may also play a major role in future therapies.
Chemokine stromal cell derived factor-1 (SDF-1, also known as CXCL12) is constitutively produced by bone marrow stromal cells and by other cells including CD34+ cells. It was initially characterized as a pre-B cell-stimulating factor and believed to be involved in retention of hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) in bone marrow. SDF-1 has been demonstrated to increase EPCs number through enhancement of (BM) c-kit+ stem cell adhesion onto extracellular matrix components by integrin receptors and protect EPCs from serum starvation-induced apoptosis. Increasing the level of SDF-1 in perepheral blood has been shown to mobilize bone marrow-derived EPCs into peripheral blood. Up-regulated SDF-1 expression in ischemic tissues or increasing SDF-1 expression in ischemic tissues through several established methods could also mobilize bone marrow-derived EPCs into peripheral blood and mediate them home to the site of neovascularization in ischemic tissues. Recently, studies had shown that the expression of SDF-1αwas up-regulated in injured carotid arteries of apoE-/- mice, which resulted in a marked mobilization of circulating Sca-1+lineage- progenitor cells (PBPCs) in the peripheral blood and mediated these cells home to the site of neointimal lesions, where they can adopt an SMC-like phenotype. It is not clear whether the up-regulation of SDF-1αcould also induce a mobilization of EPCs and mediate them home to site of injured arteries.
In the present study, we attempted to demonstrate that SDF-1 is a biological function modificator of EPCs. For this purpose, we evaluated the effects of SDF-1 on the number, proliferation, migration, adhesiveness and apoptosis of murine bone marrow-derived EPCs. To clarify the role of local SDF-1αin repair of injured artery, we investigated the effect of up-regulated SDF-1αexpression on mobilization of EPCs in peripheral blood with fluorescence-activated cell sorter analysis after wire-induced arterial injury in mice. Furthermore, spleen-derived EPCs co-cultured with AMD3100 (a highly selective antagonist of SDF-1 that binds to its receptor, CXCR4) were injected into mice after carotid injury to evaluate the effect of local SDF-1αexpression on homing of EPCs to the site of endothelial denudation.
2. Methods:
In part one, mononuclear cells (MNCs) in murine bone marrow were isolated by density gradient centrifugation and bone marrow-derived EPCs were cultured according to previously described techniques. Murine bone marrow-derived EPCs were characterized as adherent cells double positive for DiLDL-uptake and lectin binding by direct fluorescent staining under an inverted fluorescent microscope and further documented by demonstrating the expression of Sca-1 and VEGFR-2 by flow cytometer. To investigate the potential effects of SDF-1 on EPCs biological functions, bone marrow mononuclear cells or bone marrow-derived EPCs were stimulated with different concentrations of SDF-1 (1 ng/ml,10 ng/ml or 100 ng/ml) for different times. EPCs number, proliferation, migration, adhesion and apoptosis were evaluated by counting the double positive cells, MTT assay, modified Boyden chamber assay, counting the adherent cells and TUNEL staining, respectively.
In part two, we established an injury model of the mouse carotid artery with a non- microscopical surgery method. The specimens of carotid arteries 30 minutes after the denuding procedure were examined using scanning electron microscopy, and the intimal lesion 2 weeks after injury was measured with pathological method. SDF-1αwas detected by RT-PCR and Western blot in carotid arteries of mice at different time points (day 0, day 1, day 3, day 7,day14) after wire-induced injury. Peripheral blood murine samples and bone marrow were obtained from mice at different time points after induction of vascular injury or sham operation (day 0, day 1, day 3, day 7, day 14). SDF-1 determination in peripheral blood and bone marrow samples was performed by SDF-1 enzyme-linked immunosorbent assay (ELISA) kit. EPCs were quantified in peripheral blood samples by flow cytometry. EPCs were also examined in peripheral blood samples of mice in subgroups, in which blocking SDF-1 monoclonal antibody or IgG1 isotype control was injected after vascular injury. Moreover, reendothelialization was determined by Evans blue staining in a whole vessel preparation 14 days after induction of endothelial cell damage in subgroups.
In part three, mice received either 1x106 Dil-Ac-LDL–labeled spleen-derived EPCs or 1x106 CXCR4-blocked EPCs by direct percutaneous intracardial injection after induction of arterial injury. Control animals received a corresponding amount of normal saline. Thirty minutes before euthanasia, mice received FITC-labeled lectin intravenously. A subset of these animals received an injection of Evans blue dye 10 minutes before tissue harvesting. Carotid arteries were harvested 14 days after wire injury. Some of them were sectioned for fluorescent microscopic analysis to investigate Dil-Ac-LDL positive cells and lectin expression. A subset of carotid arteries was opened longitudinally for en face microscopy to examine Dil-Ac-LDL positive cells or to measure the area of reendothelialization. H&E staining was performed for morphometric analyses, and Lucia Measurement software was used to measure external elastic lamina, internal elastic lamina, and lumen circumference as well as medial and neointimal area of carotid arteries in all sections.
3. Results:
Part one:
After 7 days in endothelial cell selection medium, bone marrow mononuclear cells turned into spindle-shaped, endothelial cell-like cells. Most of them showed uptake of ac-LDL and lectin binding, demonstrating endothelial cell characteristics. These cells were characterized further by demonstrating the expression of the mouse stem-cell marker Sca-1 as well as the endothelial cell lineage antigen VEGFR-2 by flow cytometry. Endothelial cell lineage antigen CD31, eNOS and vWF were also expressed by most of these cells in immunohistochemical analysis. Counting double fluorescent staining positive cells revealed that incubation of bone marrow mononuclear cells with SDF-1αincreased the number of differentiated, adherent EPCs in a concentration-dependent manner. Data in MTT assay showed that the proliferative activity of bone marrow-derived EPCs was improved concentration-dependently by SDF-1α. Pre-exposed to SDF-1α, the adhesive activity of EPCs was increased in a concentration-dependent manner. A dose-dependent decrease of apoptosis, which was induced by paclitaxel or serum absent media, was noticed as EPCs was incubated with SDF-1α. Data revealed that SDF-1αcould mediate obvious EPCs migration in a dose-dependent manner.
Part two:
Complete removal of the endothelium was achieved with a non-microscopical surgery method. Detected with Scanning electron microscopy, a platelet monolayer covered the denuded surface of injured carotid arteries. 2 weeks later, obvious neointimal hyperplasia was noticed in the injured carotid arteries. The results in RT-PCR and western blotting showed that up-regulation of SDF-1αmRNA and protein were already evident at 1day, and peak expression was achieved at 3 days after arterial injury. In enzyme-linked immunosorbent assay, an obvious rise in plasmatic concentration of SDF-1αwas also noticed 1 day, 3 days and 7 days after carotid injury, compared with the sham operation group (P<0.01). In contrast, a significant reduction of SDF-1αbone marrow concentration was examined 1 day, 3 days and 7 days after carotid injury, compared with the sham operation group (P<0.01). The results in fluorescence-activated cell sorting analysis showed that the amount of circulating EPCs was increased markedly 1 day, 3 days and 7 days after induction of vascular injury, compared with the sham operation group (P<0.01). In a subgroup in which blocking SDF-1αmonoclonal antibody was injected, the amount of circulating EPCs was increased lightly only at 1 day after induction of vascular injury, compared with the sham operation group (P<0.05). Interestingly, Evans blue staining showed that the reendothelialization area in the SDF-1 mAb-treated group was reduced significantly 14 days after induction of endothelial cell damage, compared with the IgG1 isotype control group (P<0.01). Surprisingly, a reduced reendothelialization in the SDF-1 mAb-treated group was not associated with an increased neointima formation, compared with the IgG1 isotype control group (P>0.05).
Part three:
In modified Boyden chamber assay, pretreatment of bone marrow-derived EPCs with 10 ng/ml AMD3100 almost completely blocked cell migration in response to 100 ng/mL SDF-1α, compared with the control (P>0.05). En face microscopy 14 days after induction of injury revealed that infusion of CXCR4-free EPCs resulted a more number of cells attached at the injury site, forming islets of transplanted cells within the deendothelialized area, compared with the group treated with CXCR4-blocked EPCs (P<0.01). Immunohistochemical analysis revealed that transfused CXCR4-free EPCs were predominantly found at the injury site, lining the intraluminal margin of the neointima. Lectin staining revealed that the attaching cells at the site of endothelial injury were lectin-positive. Overlay experiments clearly demonstrated the endothelial phenotype of transfused cells. In the CXCR4-blocked EPCs transfusion group, only few Dil-Ac-LDL- and lectin-positive cells were present, and the endothelial cell line of the neointima appeared disrupted at day 14 after induction of injury compared with the CXCR4-free EPCs treatment group. In the placebo group, a few endogenous (lectin-positive, Dil-Ac-LDL–negative) endothelial cells were present at the site of endothelial denudation, and no endothelial cell line was formed. Data in Evans blue staining revealed that transfusion of CXCR4-free EPCs was associated with a significant increase in reendothelialization area compared with the placebo group (P<0.01). But no significant increase in reendothelialization area was noted in the group of CXCR4-blocked EPCs transfusion, compared with the placebo group (P>0.05). Computer-based morphometric analysis showed that the accelerated reendothelialization after transfusion CXCR4-free EPCs was associated with a significant reduction of neointima formation compared with the placebo group (P<0.01); no change in neointima formation was detected in CXCR4-blocked EPCs treated group compared with the placebo group (P>0.05).
4. Conclusions:
1. SDF-1αcould induce EPCs migration in a dose-dependent manner, and improved the proliferative and adhesive activity of EPCs, and inhibited EPCs apoptosis in the same manner. Moreover, SDF-1αcould induce differentiation of hematopoietic stem cells toward EPCs.
2. Up-regulated SDF-1 expression after vascular injury participateded in the mobilization of EPCs through changing the gradient of SDF-1 concentration between the peripheral blood and the bone marrow. Blocking EPCs mobilization mediated by SDF-1 after vascular injury could inhibit reendothelialization of injured arteries.
3. Local SDF-1 expression in injured arteries could mediate EPCs home to the site of endothelial denudation and participate in reendothelialization of neointimal lesions.
4. Bone marrow-derived EPCs of mice can be obtained through culturing bone marrow mononuclear cells in endothelial cell selection medium.
5. Carotid artery injury model of mouse can be established by a non-microscopical surgery method.
引文
1. Bennett MR, O’Sullivan MO. Mechanisms of angioplasty and stent restenosis: implications for design of rational therapy. Pharmacol Ther. 2001; 91: 149–166.
2. Bennett MR. In-stent stenosis: pathology and implications for the development of drug eluting stents. Heart. 2003 Feb;89(2):218-24.
3. Rigattieri S, Patrizi R, Silvestri P, Di Russo C, Musto C, Ferraiuolo G, et al. Very late thrombosis of a drug-eluting stent deployed during primary angioplasty for ST-elevation myocardial infarction. J Cardiovasc Med (Hagerstown). 2006 Oct;7(10):771-774.
4. El-Bialy A, Shenoda M, Caraang C. Refractory coronary vasospasm following drug-eluting stent placement treated with cyproheptadine. J Invasive Cardiol. 2006 Feb;18(2):E95-8.
5. Slavin L, Chhabra A, Tobis JM. Drug-eluting stents: preventing restenosis. Cardiol Rev. 2007 Jan-Feb;15(1):1-12.
6. Ligthart S, Vlemmix F, Dendukuri N, Brophy JM. The cost-effectiveness of drug-eluting stents: a systematic review. CMAJ. 2007 Jan 16; 176(2):199-205.
7. Skyttberg N, Linder R, Carlsson J. Drug-eluting stents can increase the risk of late stent thrombosis. Lakartidningen. 2006 Sep 27-Oct 3; 103(39):2845-7.
8. Movahed MR, Vu J, Ahsan C. Simultaneous subacute stent thrombosis of two drug-eluting stents in the left anterior descending and the circumflex coronary arteries. Case report and review of the literature. J Invasive Cardiol. 2006 Jul; 18(7):E198-202.
9. Feres F, Costa JR Jr, Abizaid A. Very late thrombosis after drug-eluting stents. Catheter Cardiovasc Interv. 2006 Jul; 68(1):83-8.
10. Li Y, Fukuda N, Kunimoto S, Yokoyama S, Hagikura K, Kawano T, Takayama T, Honye J, Kobayashi N, Mugishima H, Saito S, Serie K. Stent-based delivery of antisense oligodeoxynucleotides targeted to the PDGF A-chain decreases in-stent restenosis of the coronary artery. J Cardiovasc Pharmacol. 2006 Oct;48(4):184-90.
11. Kappert K, Sparwel J, Sandin A, Seiler A, Siebolts U, Leppanen O, Rosenkranz S, Ostman A. Antioxidants relieve phosphatase inhibition and reduce PDGF signaling incultured VSMCs and in restenosis. Arterioscler Thromb Vasc Biol. 2006 Dec;26(12):2644-51.
12. Levitzki A. PDGF receptor kinase inhibitors for the treatment of restenosis. Cardiovasc Res. 2005 Feb 15;65(3):581-6.
13. Serruys PW, Heyndrickx GR, Patel J, Cummins PA, Kleijne JA, Clowes AW. Effect of an anti-PDGF-beta-receptor-blocking antibody on restenosis in patients undergoing elective stent placement. Int J Cardiovasc Intervent. 2003;5(4):214-22.
14. Post MJ, Laham RJ, Kuntz RE, Novicki D, Simons M. The effect of intracoronary fibroblast growth factor-2 on restenosis after primary angioplasty or stent placement in a pig model of atherosclerosis. Clin Cardiol. 2002 Jun;25(6):271-8.
15. Chang Y, Ceacareanu B, Zhuang D, Zhang C, Pu Q, Ceacareanu AC, Hassid A. Counter-regulatory function of protein tyrosine phosphatase 1B in platelet-derived growth factor- or fibroblast growth factor-induced motility and proliferation of cultured smooth muscle cells and in neointima formation. Arterioscler Thromb Vasc Biol. 2006 Mar; 26(3): 501-7.
16. Camozzi M, Zacchigna S, Rusnati M, Coltrini D, Ramirez-Correa G, Bottazzi B, Mantovani A, Giacca M, Presta M. Pentraxin 3 inhibits fibroblast growth factor 2-dependent activation of smooth muscle cells in vitro and neointima formation in vivo. Arterioscler Thromb Vasc Biol. 2005 Sep;25(9):1837-42.
17. Otsuka G, Agah R, Frutkin AD, Wight TN, Dichek DA. Transforming growth factor beta 1 induces neointima formation through plasminogen activator inhibitor-1-dependent pathways. Arterioscler Thromb Vasc Biol. 2006 Apr;26(4):737-43.
18. Ando H, Fukuda N, Kotani M, Yokoyama S, Kunimoto S, Matsumoto K, Saito S, Kanmatsuse K, Mugishima H. Chimeric DNA-RNA hammerhead ribozyme targeting transforming growth factor-beta 1 mRNA inhibits neointima formation in rat carotid artery after balloon injury. Eur J Pharmacol. 2004 Jan 12;483(2-3):207-14.
19. Schober A, Knarren S, Lietz M, Lin EA, Weber C. Crucial role of stromal cell-derived factor-1alpha in neointima formation after vascular injury in apolipoprotein E-deficient mice. Circulation. 2003; 108(20):2491-2497.
20. Zernecke A, Schober A, Bot I, von Hundelshausen P, Liehn EA, Mopps B, et al.SDF-1alpha/CXCR4 axis is instrumental in neointimal hyperplasia and recruitment of smooth muscle progenitor cells. Circ Res. 2005; 96(7):784-791.
21. Liuzzo JP, Ambrose JA, Coppola JT. Sirolimus- and taxol-eluting stents differ towards intimal hyperplasia and re-endothelialization. J Invasive Cardiol. 2005 Sep;17(9):497-502.
22. Behrendt D, Ganz P. Endothelial function: from vascular biology to clinical applications. Am J Cardiol. 2002; 90 (suppl): 40L-48L.
23. Pauleto P, Sartore S, Pessina AC. Smooth muscle-cell proliferation and differentiation in neointima formation and vascular restenosis. Clin Sci. 1994; 87: 467-479.
24. Urao N, Okigaki M, Yamada H, Aadachi Y, Matsuno K, Matsui A, Matsunaga S, Tateishi K, Nomura T, Takahashi T, Tatsumi T, Matsubara H. Erythropoietin-mobilized endothelial progenitors enhance reendothelialization via Akt-endothelial nitric oxide synthase activation and prevent neointimal hyperplasia. Circ Res. 2006 Jun 9;98(11):1405-13.
25. Iwakura A, Luedemann C, Shastry S, Hanley A, Kearney M, Aikawa R, Isner JM, Asahara T, Losordo DW. Estrogen-mediated, endothelial nitric oxide synthase-dependent mobilization of bone marrow-derived endothelial progenitor cells contributes to reendothelialization after arterial injury. Circulation. 2003 Dec 23;108(25):3115-21.
26. Shariat-Madar Z, Mahdi F, Warnock M, Homeister JW, Srikanth S, Krijanovski Y, Murphey LJ, Jaffa AA, Schmaier AH.Bradykinin B2 receptor knockout mice are protected from thrombosis by increased nitric oxide and prostacyclin. Blood. 2006 Jul 1;108(1):192-9.
27. Hu H, Zhang XX, Wang YY, Chen SZ.Honokiol inhibits arterial thrombosis through endothelial cell protection and stimulation of prostacyclin. Acta Pharmacol Sin. 2005 Sep;26(9):1063-8.
28. Iwakura A, Shastry S, Luedemann C, et al. Estradiol enhances recovery after myocardial infarction by augmenting incorporation of bone marrow-derived endothelial progenitor cells into sites of ischemia-induced neovascularization via endothelial nitric oxide synthase-mediated activation of matrix metalloproteinase-9. Circulation. 2006;113:1605-14.
29. Ishizawa K, Kubo H, Yamada M, et al. Hepatocyte growth factor induces angiogenesis in injured lungs through mobilizing endothelial progenitor cells. Biochem Biophys Res Commun. 2004;324:276-80.
30. Tepper OM, Capla JM, Galiano RD, et al. Adult vasculogenesis occurs through in situ recruitment, proliferation, and tubulization of circulating bone marrow-derived cells. Blood. 2005;105:1068-77.
31. Walter DH, Rittig K, Bahlmann FH, et al. Statin therapy accelerate reendothelialization: a novel effect involving mobilization and incorporation of bone marrow-derived endothelial progenitor cells. Circulation 2002; 105: 3017-24.
32. He T, Smith LA, Harrington S, et al. Transplantation of circulating endothelial progenitor cells restores endothelial function of denuded rabbit carotid arteries. Stroke. 2004;35:2378-84.
33. Werner N, Junk S, Laufs U, et al. Intravenous transfusion of endothelial progenitor cells reduces neointima formation after vascular injury. Circ Res. 2003;93:e17-24.
34. J G, Cq W, Hh F, Hy D, Xl X, Ym X, et al. Effects of resveratrol on endothelial progenitor cells and their contributions to reendothelialization in intima-injured rats. J Cardiovasc Pharmacol. 2006 May;47(5):711-21.
35. Walter DH, Rittig K, Bahlmann FH, Kirchmair R, Silver M, Murayama T, et al. Statin therapy accelerate reendothelialization: a novel effect involving mobilization and incorporation of bone marrow-derived endothelial progenitor cells. Circulation. 2002; 105: 3017-24.
36. Natori T, Sata M, Washida M, Hirata Y, Nagai R, Makuuchi M. G-CSF stimulates angiogenesis and promotes tumor growth: potential contribution of bone marrow-derived endothelial progenitor cells. Biochem Biophys Res Commun. 2002 Oct 4;297(4):1058-61.
37. De Falco E, Porcelli D, Torella AR, et al. SDF-1 involvement in endothelial phenotype and ischemia-induced recruitment of bone marrow progenitor cells. Blood. 2004; 104: 3472-82.
38. Bonello L, Basire A, Sabatier F, Paganelli F, Dignat-George F. Endothelial injury induced by coronary angioplasty triggers mobilization of endothelial progenitor cells in patients with stable coronary artery disease. J Thromb Haemost. 2006May;4(5):979-81.
39. Gill M, Dias S, Hattori K, Rivera ML, Hicklin D, Witte L, et al. Vascular trauma induces rapid but transient mobilization of VEGFR2(+)AC133(+) endothelial precursor cells. Circ Res. 2001 Feb 2;88(2):167-74.
40. Scheubel RJ, Zorn H, Silber RE, Kuss O, Morawietz H, Holtz J, et al. Age-dependent depression in circulating endothelial progenitor cells in patients undergoing coronary artery bypass grafting. J Am Coll Cardiol. 2003 Dec 17;42(12):2073-80.
41. Yang Z, Wang JM, Chen L, Luo CF, Tang AL, Tao J. Acute exercise-induced nitric oxide production contributes to upregulation of circulating endothelial progenitor cells in healthy subjects. J Hum Hypertens. 2007 Mar 8; [Epub ahead of print]
42. Wahl P, Bloch W, Schmidt A. Exercise has a Positive Effect on Endothelial Progenitor Cells, which Could be Necessary for Vascular Adaptation Processes. Int J Sports Med. 2006 Nov 16; [Epub ahead of print]
43. Laufs U, Urhausen A, Werner N, Scharhag J, Heitz A, Kissner G, Bohm M, Kindermann W, Nickenig G. Running exercise of different duration and intensity: effect on endothelial progenitor cells in healthy subjects. Eur J Cardiovasc Prev Rehabil. 2005 Aug;12(4):407-14.
44. He T, Smith LA, Harrington S, Nath KA, Caplice NM, Katusic ZS. Transplantation of circulating endothelial progenitor cells restores endothelial function of denuded rabbit carotid arteries. Stroke. 2004;35:2378-84.
45. Griese DP, Ehsan A, Melo LG, Kong D, Zhang L, Mann MJ, , et al. Isolation and Transplantation of Autologous Circulating Endothelial Cells Into Denuded Vessels and Prosthetic Grafts. Circulation. 2003;108:2710.
46. Wassmann S, Werner N, Czech T, Nickenig G. Improvement of endothelial function by systemic transfusion of vascular progenitor cells. Circ Res. 2006 Oct 13;99(8):e74-83.
47. Yamaguchi J, Kusano KF, Masuo O, et al. Stromal cell-derived factor-1 effects on ex vivo expanded endothelial progenitor cells recruitment for ischemic neovascularization. Circulation. 2003; 107:1322-1328.
48. Hiasa K, Ishibashi M, Ohtani K, et al. Gene transfer of stromal cell-derived factor-1alpha enhances ischemic vasculogenesis and angiogenesis via vascular endothelial growth factor/endothelial nitric oxide synthase-related pathway:next-generation chemokine therapy for therapeutic neovascularization. Circulation.2004; 109: 2454–61.
49. Moore M.A, Hattori K, Heissig B, et al. Mobilization of endothelial and hematopoietic stem and progenitor cells by adenovector-mediated elevation of serum levels of SDF-1, VEGF, and angiopoietin-1, Ann N Y Acad Sci. 2001; 938: 36–45.
50. Aiuti A, Turchetto L, Cota M, et al. Human CD34+ cells express CXCR4 and its ligand stromal cell-derived factor-1. Implications for infection by T-cell tropic human immunodeficiency virus. Blood. 1999;94:62-73.
51. Walter DH, Haendeler J, Reinhold J, Rochwalsky U, Seeger F, Honold J, Hoffmann J, Urbich C, Lehmann R, Arenzana-Seisdesdos F, Aicher A, Heeschen C, Fichtlscherer S, Zeiher AM, Dimmeler S. Impaired CXCR4 signaling contributes to the reduced neovascularization capacity of endothelial progenitor cells from patients with coronary artery disease. Circ Res. 2005 Nov 25;97(11):1142-51.
52. Smadja DM, Bieche I, Uzan G, Bompais H, Muller L, Boisson-Vidal C, Vidaud M, Aiach M, Gaussem P. PAR-1 activation on human late endothelial progenitor cells enhances angiogenesis in vitro with upregulation of the SDF-1/CXCR4 system. Arterioscler Thromb Vasc Biol. 2005 Nov;25(11):2321-7.
53. Lataillade JJ, Domenech J, Le Bousse-Kerdiles MC. Stromal cell-derived factor-1 (SDF-1)\CXCR4 couple plays multiple roles on haematopoietic progenitors at the border between the old cytokine and new chemokine worlds: survival, cell cycling and trafficking. Eur Cytokine Netw. 2004;15:177-88.
54. Frenette PS, Weiss L. Sulfated glycans induce rapid hematopoietic progenitor cell mobilization:evidence for selectin dependent and independent mechanisms. Blood. 2000; 96 (7) :2460.
55. Hattori K, Heissig B , Tashiro K, et al. Plasma elevation of stromal cell-derived factor-1 induces mobilization of mature and immature hematopoietic progenitor and stem cells. Blood. 2001; 97 :3354 - 3360.
56. Kalka C, Masuda H, Takahashi T, et al. Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. Proc Natl Acad Sci USA. 2000; 97: 3422-7.
57. Vasa M, Fichtlscherer S, Aicher A, et al. Number and migratory activity of circulatingendothelial progenitor cells inversely correlate with risk factors for coronary artery disease. Circ Res. 2001; 89: E1-7.
58. Gensch C, Clever Y, Werner C, Hanhoun M, Bohm M, Laufs U.Regulation of endothelial progenitor cells by prostaglandin E1 via inhibition of apoptosis. J Mol Cell Cardiol. 2007 Mar; 42(3):670-7.
59. Gensch C, Clever YP, Werner C, Hanhoun M, Bohm M, Laufs U.The PPAR-gamma agonist pioglitazone increases neoangiogenesis and prevents apoptosis of endothelial progenitor cells. Atherosclerosis. 2006 Jul 27; [Epub ahead of print]
60. Hill JM, Zalos G, Halcox JP, et al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med. 2003; 348: 593-600.
61. Schmidt-Lucke C, Rossig L, Fichtlscherer S, et al. Reduced number of circulating endothelial progenitor cells predicts future cardiovascular events: proof of concept for the clinical importance of endogenous vascular repair. Circulation. 2005;111:2981-7.
62. 崔斌 黄岚 宋耀明 李爱民 晋军 覃军 于学军 耿召华。冠心病患者循环内皮祖细胞 与 相 关 危 险 因 素 及 冠 状 动 脉 病 变 的 关 系 。 中 华 心 血 管 病 杂 志 。2006;33(9):785-788。
63. Valgimigli M, Rigolin GM, Fucili A, et al. CD34+ and endothelial progenitor cells in patients with various degrees of congestive heart failure. Circulation. 2004;110:1209-12.
64. Edelberg JM, Tang L, Hattori K, et al. Young adult bone marrow-derived endothelial precursor cells restore aging-impaired cardiac angiogenic function. Circ Res. 2002;90:E89-93.
65. Yamamoto K, Kondo T, Suzuki S, et al. Molecular evaluation of endothelial progenitor cells in patients with ischemic limbs: therapeutic effect by stem cell transplantation. Arterioscler Thromb Vasc Biol. 2004;24:e192-6.
66. Deb A, Wang SH, Skelding K, et al. Bone marrow-derived myofibroblasts are present in adult human heart valves. J Heart Valve Dis. 2005;14:674-8.
67. Nagasawa T, Kikutani H, Kishimoto T. Molecular cloning and structure of a pre-B-cell-growth stimulating factor. Proc Natl Acad Sci U S A. 1994;91:2305-9.
68. Kozuka T, Ishimaru F, Fujii K, Masuda K, Kaneda K, Imai T, Fujii N, Ishikura H, Hongo S, Watanabe T, Shinagawa K, Ikeda K, Niiya K, Harada M, TanimotoM.Plasma stromal cell-derived factor-1 during granulocyte colony-stimulating factor-induced peripheral blood stem cell mobilization. Bone Marrow Transplant. 2003 Apr;31(8):651-4.
69. Hattori K, Heissig B, Tashiro K, Honjo T, Tateno M, Shieh JH, Hackett NR, Quitoriano MS, Crystal RG, Rafii S, Moore MA.Plasma elevation of stromal cell-derived factor-1 induces mobilization of mature and immature hematopoietic progenitor and stem cells. Blood. 2001 Jun 1;97(11):3354-60.
70. Lataillade JJ, Clay D, Dupuy C, Rigal S, Jasmin C, Bourin P, et al. Chemokine SDF-1 enhances circulating CD34+ cell proliferation in synergy with cytokines: possible role in progenitor survival. Blood. 2000;95:756-68.
71. Gotoh A, Miyazawa K, Yaguchi M, Broxmeyer H. Priming with SDF-1 induces enhancement of cytokine-dependent survival effect and pronounced activation of MAP kinase signaling in hematopoietic cells. Blood. 1998;92:200a.
72. Burger JA, Tsukada N, Burger M, Zvaifler NJ, Dell'Aquila M, Kipps T. Blood-derived nurse-like cells protect chronic lymphocytic leukemia B cells from spontaneous apoptosis through stromal cell-derived factor-1. Blood. 2000;96:2655-63.
73. Kollet O, Grabovsky V, Franitza S, Lider O, Alon R, Lapidot T. SDF-1 induces survival, adhesion, and migration in 3D ECM like gels of murine CXCR-4null fetal liver cells via another GPCR . Blood. 2000;96:65a.
74. 陈剑飞, 黄岚, 晋军 武晓静 刘兰 周健 赵晓晖 崔斌。年龄对大鼠骨髓内皮祖细胞数量和功能的影响及其意义。中华心血管病杂志。2006;34(11):1026-8.
75. Hamada H, Kim MK, Iwakura A, Ii M, Thorne T, Qin G, Asai J, Tsutsumi Y, Sekiguchi H, Silver M, Wecker A, Bord E, Zhu Y, Kishore R, Losordo DW. Estrogen receptors alpha and beta mediate contribution of bone marrow-derived endothelial progenitor cells to functional recovery after myocardial infarction. Circulation. 2006 Nov 21;114(21):2261-70.
76. Ohta T, Kikuta K, Imamura H, Takagi Y, Nishimura M, Arakawa Y, Hashimoto N, Nozaki K. Administration of ex vivo-expanded bone marrow-derived endothelial progenitor cells attenuates focal cerebral ischemia-reperfusion injury in rats. Neurosurgery. 2006 Sep; 59(3):679-86.
77. Strehlow K, Werner N, Berweiler J, Link A, Dirnagl U, Priller J, et al. Estrogenincreases bone marrow–derived endothelial progenitor cell production and diminishes neointima formation. Circulation. 2003;107:3059-3065.
78. Zhao YD, Courtman DW, Deng Y, Kugathasan L, Zhang Q, Stewart DJ. Rescue of monocrotaline-induced pulmonary arterial hypertension using bone marrow-derived endothelial-like progenitor cells: efficacy of combined cell and eNOS gene therapy in established disease. Circ Res. 2005 Mar 4;96(4):442-50.
79. Kong D, Melo LG, Mangi AA, Zhang L, Lopez-Ilasaca M, Perrella MA, et al. Enhanced inhibition of neointimal hyperplasia by genetically engineered endothelial progenitor cells. Circulation. 2004;109:1769-1775.
80. Dimmeler S, Aicher A, Vasa M, Mildner-Rihm C, Adler K, Tiemann M, et al. HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI 3-kinase/Akt pathway. J Clin Invest. 2001; 108(3):391-397.
81. Hyun-Jai C, Hyo-Soo K, Myoung-Mook L, Dae-Hee K, Hyun-Ju Y, Jin H, et al. Mobilized endothelial progenitor cells by granulocyte-macrophage colony-stimulating factor accelerate reendothelialization and reduce vascular inflammation after intravascular radiation. Circulation. 2003;108:2918.
82. Jin H, Chang-Hwan Y, Hyo-Soo K, Jin-Ho C, Hyun-Jae K, Kyung-Kook H, et al. Characterization of two types of endothelial progenitor cells and their different contributions to neovasculogenesis. ATVB. 2004;24:288.
83. Jun-Hui Z, Qian-Min T, Jun-Zhu C, Xing-Xiang W, Jian-Hua Z, Yun-Peng S, et al. Statins contribute to enhancement of the number and the function of endothelial progenitor cells from peripheral blood. Acta Physiologica Sinica. 2004;56(3):357-364.
84. Jun-hui Z, Xing-xiang W, Jun-zhu C, Yun-peng S, Jian-hua Z, Xiao-gang G, et al. Effects of puerarin on number and activity of endothelial progenitor cells from peripheral blood. Acta Pharmacologica Sinica. 2004;25(8):1045-1051.
85. Zemani F, Benisvy D, Galy-Fauroux I, Lokajczyk A, Colliec-Jouault S, Uzan G, et al. Low-molecular-weight fucoidan enhances the proangiogenic phenotype of endothelial progenitor cells. Biochemical Pharmacology. 2005;70(8) :1167-1175.
86. Jun Zhu C, Fu Rong Z, Qian Min T, Xing Xiang W, Jian Hua Z,Jun Hui Z. Number and activity of endothelial progenitor cells from peripheral blood in patients with hypercholesterolaemia. Clinical Science. 2004;107, 273–280.
87. Verma S, Kuliszewski MA, Shu-Hong L, Szmitko PE, Zucco L, Chao-Hung W, et al. C-Reactive Protein Attenuates Endothelial Progenitor Cell Survival, Differentiation, and Function. Circulation. 2004;109:2058-2067.
88. Zhou B, Cao XC, Fang ZH, Zheng CL, Han ZB, Ren H, Poon MC, Han ZC. Prevention of diabetic microangiopathy by prophylactic transplant of mobilized peripheral blood mononuclear cells. Acta Pharmacol Sin. 2007 Jan;28(1):89-97.
89. Sales VL, Engelmayr GC Jr, Mettler BA, Johnson JA Jr, Sacks MS, Mayer JE Jr. Transforming growth factor-beta1 modulates extracellular matrix production, proliferation, and apoptosis of endothelial progenitor cells in tissue-engineering scaffolds. Circulation. 2006 Jul 4;114(1 Suppl):I193-9.
90. Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenisis. Science. 1997;275:964-967.
91. 赵晓辉,黄岚,尹扬光,周健,方玉强,朱光旭,陈剑飞,崔斌。雌二醇对骨髓内皮祖细胞部分生物学功能的影响。中华老年心脑血管病杂志。2005; 8 (5):343-345。
92. Campbell JJ, Hedrick J, Zlotnik A, et al.Chemokines and the Arrest of Lymphocytes Rolling Under Flow Conditions, Scince. 1998;279:381-384.
93. Peled A, Grabovsky V, Habler L, et al. The chemokine SDF-1 stimulates integrin-mediated arrest of CD34 ( + ) cells on vascular endothelium under shear flow. J Clin Invest. 1999; 104 (9) :1199.
94. Peled A, Kollet O, Ponomaryov T, et al. The chemokine SDF-1 activates the integrins LFA-1, VLA-4, and VLA-5 on immature human CD34 + cells: role in transendothelial/stromal migration and engraftment of NOD/SCID mice. Blood. 2000; 95 :3289 – 3296.
95. Mohle R, Bautz F, Shalhin R, et al. The chemokine receptor CXCR4 is expressed on CD34+ hematopoietic progenitor and leukemia cells and mediates transendothelial migration induced by stromal cell-derivedfactor-1.Blood. 1998; 91 (12) :4523 - 4530.
96. Aiuti A, Webb IJ, Bleul C, et al. The chemokine SDF-1 is a chemoattractant for human CD34+hematopoietic progenitor cells and provides a new mechanism to explain the mobilization of CD34+ progenitors to peripheria blood. J Exp Med. 1997; 185 (1) :111 - 120.
97. Lataillade JJ, Clay D, Bourin P, et al. Stromal cell-derived factor 1 regulates primitive hematopoiesis by suppressing apoptosis and by promoting G(0)/G(1) transition in CD34(+) cells: evidence for an autocrine/paracrine mechanism. Blood. 2002; 99: 1117-29.
98. Lindner V, Fingerle J, Reidy MA. Mouse model of arterial injury. Circ Res. 1993; 73: 792–796.
99. Ma J, Ge J, Zhang S, Sun A, Shen J, Chen L, et al. Time course of myocardial stromal cell-derived factor 1 expression and beneficial effects of intravenously administered bone marrow stem cells in rats with experimental myocardial infarction. Basic Res Cardiol. 2005; 100: 217-223.
100. Abi-Younes S, Sauty A, Mach F, Sukhova GK, Libby P, Luster AD. The Stromal Cell–Derived Factor-1 Chemokine Is a Potent Platelet Agonist Highly Expressed in Atherosclerotic Plaques. Circulation Research. 2000;86:131.
101. Kim YS, Bigliani LU, Fujisawa M, Murakami K, Chang SS, Lee HJ, Lee FY, Blaine TA. Stromal cell-derived factor 1 (SDF-1, CXCL12) is increased in subacromial bursitis and downregulated by steroid and nonsteroidal anti-inflammatory agents. J Orthop Res. 2006 Aug; 24(8):1756-64.
102. Togel F, Isaac J, Hu Z, Weiss K, Westenfelder C. Renal SDF-1 signals mobilization and homing of CXCR4-positive cells to the kidney after ischemic injury. Kidney Int. 2005 May; 67(5):1772-84.
103. Werner N, Priller J, Laufs U, et al. Bone marrow-derived progenitor cells modulate vascular reendothelialization and neointimal formation: effect of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibition. Arterioscler. Thromb Vasc Biol. 2002; 22: 1567-72.
104. Papayannopoulou T, Current mechanistic scenarios in hematopoietic stem/progenitor cell mobilazation. Blood. 2004;103:1580-1585.
105. Vaday GG, Lider O. Extracellular matrix moieties , cytokines , and enzymes: dynamic effects on immune cell behavior and inflammation. J Leukoc Biol. 2000; 67 :149-159.
106. Petit I, Kravitz MS, Nagler A, et al. G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and upregulating CXCR4. Nature Immunol. 2002; 3 (5) :687.
107. Levesque LJ, Bendall J, Hendy B, et al. SDF-1 is inactivated by proteolytic cleavage in the bone marrow of mice mobilized by either G-CSF or cyclophosphamide. Blood. 2001; 98(4) : 831.
108. Delgado M, Lewis IC, Loetscher P, et al. Rapid inactivation of stromal cell-derived factor-1 by cathepsin G associated with lymphocytes. Eur J Immunol. 2001; 31 (6) :699.
109. Levesque JP, Hendy J, Takamatsu Y, et al. Disruption of the CXCR4/CXCL12 chemotactic interaction during hematopoietic stem cell mobilization induced by G-CSF or cyclophosphamide. J Clin Invest. 2003; 111 :187-196.
110. Voermans C, Kooi ML, Rodenhui S, et al. In vitro migratory capacity of CD34+cells is related to hematopoietic recovery after autologous stem cell transplantation. Blood. 2001; 97 (3) :799.
111. Dabusti M, Lanza F, Campioni D, et al. CXCR-4 expression on bone marrow CD34+cells prior to mobilization can predict mobilization adequacy in patients with hematologic malignancies. Hematol Stem Cell Res. 2003; 12(4) :425-434.
112. Perez LE, Alpdogan O, Shieh JH, et al.Increased plasma levels of stromal-derived factor-1 (SDF-1/CXCL12) enhance human thrombopoiesis and mobilize human colony-forming cells (CFC) in NOD/SCID mice. Exp Hematol. 2004 Mar;32(3):300-7.
113. Pelus LM, Bian H, Fukuda S, et al. The CXCR4 agonist peptide, CTCE-0021, rapidly mobilizes polymorphonuclear neutrophils and hematopoietic progenitor cells into peripheral blood and synergizes with granulocyte colony-stimulating factor. Exp Hematol. 2005 Mar;33(3):295-307.
114. Sweeney EA, Lortat-Jacob H, Priestley GV, et al. Sulfated polysaccharides increase plasma levels of SDF-1 in monkeys and mice: involvement in mobilization of stem/progenitor cells. Blood. 2002 Jan 1;99(1):44-51.
115. Nagano M, Yamashita T, Hamada H, Ohneda K, Kimura KI, Nakagawa T, Shibuya M, Yoshikawa H, Ohneda O. Identification of functional endothelial progenitor cells suitable for the treatment of ischemic tissue using human umbilical cord blood. Blood. 2007 Mar 22; [Epub ahead of print]
116. Lee SP, Youn SW, Cho HJ, Li L, Kim TY, Yook HS, Chung JW, Hur J, Yoon CH, Park KW, Oh BH, Park YB, Kim HS. Integrin-linked kinase, a hypoxia-responsivemolecule, controls postnatal vasculogenesis by recruitment of endothelial progenitor cells to ischemic tissue. Circulation. 2006 Jul 11;114(2):150-9.
117. Irie H, Tatsumi T, Takamiya M, Zen K, Takahashi T, Azuma A, Tateishi K, Nomura T, Hayashi H, Nakajima N, Okigaki M, Matsubara H. Carbon dioxide-rich water bathing enhances collateral blood flow in ischemic hindlimb via mobilization of endothelial progenitor cells and activation of NO-cGMP system. Circulation. 2005 Mar 29; 111(12): 1523-9.
118. Ii M, Nishimura H, Iwakura A, Wecker A, Eaton E, Asahara T, Losordo DW. Endothelial progenitor cells are rapidly recruited to myocardium and mediate protective effect of ischemic preconditioning via "imported" nitric oxide synthase activity. Circulation. 2005 Mar 8; 111(9): 1114-20.
119. Lapidot T, Kollet O. The essential roles of the chemokine SDF-1 and its receptor CXCR4 in human stem cell homing and repopulation of transplanted immune-deficient NOD/SCID and NOD/SCID/B2m(null) mice. Leukemia. 2002 Oct;16(10):1992-2003.
120. Peled A, Petit I, Kollet O, et al. Dependence of human stem cell engraftment and repopulation of NOD/ SCID mice on CXCR4. Science. 1999; 283 (5403):845 - 848.
121. Kim CH, Broxmeyer HJ. In vitro behavior of hematopoietic progenitor cells under the influence of chemoattractants: stromal cell-derived factor-1, steel factor, and the bone marrow enviroment. Blood. 1998; 91(1):100 - 110.
122. Tan Y, Shao H, Eton D, Yang Z, Alonso-Diaz L, Zhang H, Schulick A, Livingstone AS, Yu H.Stromal cell-derived factor-1 enhances pro-angiogenic effect of granulocyte-colony stimulating factor. Cardiovasc Res. 2007 Mar 1;73(4):823-32.
1. WHO. World Health Report [EB/OL]. [2003]. http://www.who.int/whr/en/.
2. AHA. Heart disease and stroke statistics-2004 update [EB/OL]. Dallas, Tex: American Heart Association, 2003.
3. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Lancet. 1988; 2:349.
4. Peters RJ, Mehta SR, Fox KA, et al. Effects of aspirin dose when used alone or in combination with clopidogrel in patients with acute coronary syndromes: Observations from the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) Study. Circulation. 2003;108:1682.
5. Freemantle N, Cleland J, Young P, et al. Beta blockade after myocardial infarction: Systematic review and meta regression analysis. BMJ. 1999; 318:1730.
6. Dargie HJ. Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: The CAPRICORN randomised trial. Lancet. 2001; 357:1385.
7. ACE Inhibitor Myocardial Infarction Collaborative Group. Indications for ACE inhibitors in the early treatment of acute myocardial infarction: Systematic overview of individual data from 100,000 patients in randomized trials. Circulation. 1998; 97:2202.
8. Pfeffer MA. ACE inhibitors in acute myocardial infarction: Patient selection and timing. Circulation. 1998; 97:2192.
9. Pitt B, Waters D, Brown WV, et al. Aggressive lipid-lowering therapy compared with angioplasty in stable coronary artery disease. Atorvastatin versus Revascularization Treatment Investigators. N Engl J Med. 1999; 341:70–76.
10. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: A randomised placebo-controlled trial. Lancet. 2002; 360:7–22.
11. Widimsky P, Budesinsky T, Vorac D, et al. Long distance transport for primary angioplasty vs immediate thrombolysis in acute myocardial infarction. Final results ofthe randomized national multicentre trial—PRAGUE-2. Eur Heart J. 2003; 24:94.
12. Grines CL, Westerhausen DR Jr, Grines LL, et al. A randomized trial of transfer for primary angioplasty versus on-site thrombolysis in patients with high-risk myocardial infarction: The Air Primary Angioplasty in Myocardial Infarction study. J Am Coll Cardiol. 2002; 39:1713.
13. Kober L, Torp-Pedersen C, Carlsen JE, et al. A clinical trial of the angiotensin-converting- enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. Trandolapril Cardiac Evaluation (TRACE) Study Group. N Engl J Med. 1995; 333:1670,
14. The SOLVD Investigators. Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. N Engl J Med. 1992; 327:685.
15. BEST Trial Investigators. A trial of the beta-adrenergic blocker bucindolol in patients with advanced heart failure. N Engl J Med. 2001; 344:1659.
16. Bristow MR. Anti-adrenergic therapy of chronic heart failure: Surprises and new opportunities. Circulation. 2003; 107:1100.
17. Pitt B. Aldosterone blockade in patients with systolic left ventricular dysfunction. Circulation. 2003; 108:1790.
18. Pitt B, Remme W, Zannad F, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003; 348:1309.
19. Caveliers V, De Keulenaer G, Everaert H, Van Riet I, Van Camp G, Verheye S, Roland J, Schoors D, Franken PR, Schots R. In vivo visualization of (111)In labeled CD133+ peripheral blood stem cells after intracoronary administration in patients with chronic ischemic heart disease. Q J Nucl Med Mol Imaging. 2007 Mar;51(1):61-6.
20. Kawamura A, Horie T, Tsuda I, Abe Y, Yamada M, Egawa H, Iida J, Sakata H, Onodera K, Tamaki T, Furui H, Kukita K, Meguro J, Yonekawa M, Tanaka S. Clinical study of therapeutic angiogenesis by autologous peripheral blood stem cell (PBSC) transplantation in 92 patients with critically ischemic limbs. J Artif Organs. 2006;9(4):226-33.
21. Chen S, Liu Z, Tian N, Zhang J, Yei F, Duan B, Zhu Z, Lin S, Kwan TW.Intracoronary transplantation of autologous bone marrow mesenchymal stem cells for ischemic cardiomyopathy due to isolated chronic occluded left anterior descending artery. J Invasive Cardiol. 2006 Nov;18(11):552-6.
22. Jiang W, Ma A, Wang T, Han K, Liu Y, Zhang Y, Dong A, Du Y, Huang X, Wang J, Lei X, Zheng X. Homing and differentiation of mesenchymal stem cells delivered intravenously to ischemic myocardium in vivo: a time-series study. Pflugers Arch. 2006 Oct;453(1):43-52.
23. Uemura R, Xu M, Ahmad N, Ashraf M. Bone marrow stem cells prevent left ventricular remodeling of ischemic heart through paracrine signaling. Circ Res. 2006 Jun 9;98(11):1414-21.
24. Krugliakov PV, Sokolova IB, Amineva KhK, Nekrasova NN, Viide SV, Cherednichenko NN, Zaritskii AIu, Semernin EN, Kisliakova TV, Polyntsev DG. Mesenchymal stem cell transplantation for myocardial reparation of rat experimental heart failure. Tsitologiia. 2004;46(12):1043-54.
25. Ozbaran M, Omay SB, Nalbantgil S, Kultursay H, Kumanlioglu K, Nart D, Pektok E. Autologous peripheral stem cell transplantation in patients with congestive heart failure due to ischemic heart disease. Eur J Cardiothorac Surg. 2004 Mar;25(3):342-50; discussion 350-1.
26. Belenkov IuN, Ageev FT, Mareev VIu, Savchenko VG. Mobilization of bone marrow stem cells in the management of patients with heart failure. Protocol and first results of ROT FRONT trial. Kardiologiia. 2003;43(3):7-12.
27. Urbanek K, Torella D, Sheikh F, De Angelis A, Nurzynska D, Silvestri F, Beltrami CA, Bussani R, Beltrami AP, Quaini F, Bolli R, Leri A, Kajstura J, Anversa P. Myocardial regeneration by activation of multipotent cardiac stem cells in ischemic heart failure. Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8692-7.
28. Kang HJ, Kim HS, Koo BK, Kim YJ, Lee D, Sohn DW, Oh BH, Park YB.Intracoronary infusion of the mobilized peripheral blood stem cell by G-CSF is better than mobilization alone by G-CSF for improvement of cardiac function and remodeling: 2-year follow-up results of the Myocardial Regeneration and Angiogenesis in Myocardial Infarction with G-CSF and Intra-Coronary Stem Cell Infusion (MAGIC Cell) 1 trial. Am Heart J. 2007 Feb;153(2): 237.e1-8.
29. Kastrup J, Ripa RS, Wang Y, Jorgensen E. Myocardial regeneration induced by granulocyte- colony-stimulating factor mobilization of stem cells in patients with acute or chronic ischaemic heart disease: a non-invasive alternative for clinical stem cell therapy? Eur Heart J. 2006 Dec;27(23):2748-54.
30. Ripa RS, Jorgensen E, Wang Y, Thune JJ, Nilsson JC, Sondergaard L, Johnsen HE, Kober L, Grande P, Kastrup J. Stem cell mobilization induced by subcutaneous granulocyte-colony stimulating factor to improve cardiac regeneration after acute ST-elevation myocardial infarction: result of the double-blind, randomized, placebo-controlled stem cells in myocardial infarction (STEMMI) trial. Circulation. 2006 Apr 25;113(16):1983-92.
31. Pompilio G, Cannata A, Peccatori F, Bertolini F, Nascimbene A, Capogrossi MC, Biglioli P. Autologous peripheral blood stem cell transplantation for myocardial regeneration: a novel strategy for cell collection and surgical injection. Ann Thorac Surg. 2004 Nov;78(5):1808-12.
32. Lee SP, Youn SW, Cho HJ, Li L, Kim TY, Yook HS, Chung JW, Hur J, Yoon CH, Park KW, Oh BH, Park YB, Kim HS. Integrin-linked kinase, a hypoxia-responsive molecule, controls postnatal vasculogenesis by recruitment of endothelial progenitor cells to ischemic tissue. Circulation. 2006 Jul 11;114(2):150-9.
33. Yoon CH, Hur J, Oh IY, Park KW, Kim TY, Shin JH, Kim JH, Lee CS, Chung JK, Park YB, Kim HS. Intercellular adhesion molecule-1 is upregulated in ischemic muscle, which mediates trafficking of endothelial progenitor cells. Arterioscler Thromb Vasc Biol. 2006 May;26(5): 1066-72.
34. Fan CL, Gao PJ, Che ZQ, Liu JJ, Wei J, Zhu DL.Therapeutic neovascularization by autologous transplantation with expanded endothelial progenitor cells from peripheral blood into ischemic hind limbs. Acta Pharmacol Sin. 2005 Sep;26(9):1069-75.
35. Ii M, Nishimura H, Iwakura A, Wecker A, Eaton E, Asahara T, Losordo DW.Endothelial progenitor cells are rapidly recruited to myocardium and mediate protective effect of ischemic preconditioning via "imported" nitric oxide synthase activity. Circulation. 2005 Mar 8;111(9):1114-20.
36. Yi C, Xia W, Zheng Y, Zhang L, Shu M, Liang J, Han Y, Guo S.Transplantation of endothelial progenitor cells transferred by vascular endothelial growth factor gene for vascular regeneration of ischemic flaps. J Surg Res. 2006 Sep;135(1):100-6.
37. Nagasawa T, Kikutani H, Kishimoto T. Molecular cloning and structure of a pre-B cell growth-stimulating factor. Proc Natl Acad Sci USA. 1994; 91: 2305 – 2309.
38. Psenak O. Stromal cell-derived factor-1(SDF-1). Its structure and function. Cas Lek Cesk. 2001; 140(12):355-363.
39. Schober A, Knarren S, Lietz M, Lin EA, Weber C. Crucial role of stromal cell-derived factor-1alpha in neointima formation after vascular injury in apolipoprotein E-deficient mice. Circulation. 2003 Nov 18; 108(20):2491-7.
40. Zernecke A, Schober A, Bot I, von Hundelshausen P, Liehn EA, Mopps B, Mericskay M, Gierschik P, Biessen EA, Weber C. SDF-1alpha/CXCR4 axis is instrumental in neointimal hyperplasia and recruitment of smooth muscle progenitor cells. Circ Res. 2005 Apr 15; 96(7): 784-91.
41. Feng Y, Broder CC, Kennedy PE, et al. HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science. 1996; 272(5263): 872-877.
42. Loetscher M, Geiser T, O′Reilly T, et al. Cloning of a human seven transmembrane domain receptor, LESTR, that is highly expressed in leukocytes. J Biol Chem, 1994 ; 269 :232-237.
43. Amara A, Lorthioir O, Valenzuela A, et al. Stromal cell-derived factor-1 associates with heparan sulfates through the first beta-strand of the chemokine. J Biol Chem. 1999; 274: 23916.
44. Nagasawa T, Hirota S, Tachibana K, et al. Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in m ice lacking the CXC chemokine PBSF/SDF-1. Nature. 1996; 382(6592): 635-638.
45. Zou YR, Kottmann AH, Kuroda M, et a1. Function of the chemokine receptor CXCR4 in haematopoiesis and cerebellar developm ent. Nature. 1998; 393(6685):595-599.
46. Ma Q, Jones D, Springer TA. The chemokine receptor CXCR4 is required for the retention of B lineage and granulocytic precursors within the bone marrow microenvironment. Immunity. 1999;10(4):463-471.
47. Juarez J, Bcndall I, Bradstock K, et a1. Chemokines and their receptors as therapeutic targets: the role of the SDF 1/CXCR4 axis. Curr Pharm Des. 2004;10 (11):1245-1259.
48. Majka M, Ratajczak J, Kowalska MA, et a1. Binding of stromal derived factor-lα (SDF-lα) to CXCR4 chemokine receptor in normal human megakaryoblasts but not in platelets induces phosphorylation of mitogen-activated protein kinase p42/44 (MAPK),ELK-1 transcription factor and serine/threonine kinase AKT. Eur J Haematol. 2000; 64(3):164-172.
49. Vila-Coro AJ, Rodriguez-Frade JM, Martin De Ana A, et a1. The chemokine SDF-lα triggers CXCR4 receptor dimerization and activates the JAK/STAT pathway. FASEB J. 1999; 13(13): 1699-1710.
50. Fernandis AZ, Cherla RP, Ganju RK. Differential regulation of CXCR4-mediated T-cell chemotaxis and mitogen-activated protein kinase activation by the membrane tyrosine phosphatase,CD45. J Biol Chem. 2003; 278(11): 9536-9543.
51. Majka M, Janowska-Wieczorek A, Ratajezak J, et a1. Stromal-derived factor 1 and thrombopoietin regulate distinct aspects of hum an megakaryopoiesis. Blood. 2000; 96(13): 4142-4151.
52. Zhang XF, W ang JF, Matczak E, et a1. Janus kinase 2 is involved in stromal cell-derived factor-1 alpha-induced tyrosine phosphorylation of focal adhesion proteins and migration of hematopoietic progenitor cells. Blood. 2001; 97(11): 3342-3348.
53. Kim CH, Hangoc G, Cooper C, et a1. Altered responsiveness to chemokines due to targeted disruption of SHIP. J Clin Invest. 1999; 104(12): 1751-1759.
54. Kim CH,Qu CK, Hangoc G,et a1. Abnormal Chemokine-induced Responses of Immature and Mature Hematopoietic Ce11s from Motheaten Mice Implicate the Protein Tyrosine Phosphatase SHP-1 in Chemokine Responses. J Exp Med. 1999; 190(5): 681—690.
55. Chernock RD, Cherla RP, Ganju RK. SHP2 and cbl participate in a-chemokine receptor CXCR4-mediated signaling pathways. Blood. 2001; 97(3): 608-615.
56. Papayannopoulou T, Current mechanistic scenarios in hematopoietic stem/progenitor cell mobilazation. Blood. 2004; 103: 1580-1585.
57. Vaday GG, Lider O. Extracellular matrix moieties , cytokines , and enzymes: dynamic effects on immune cell behavior and inflammation. J Leukoc Biol. 2000 ; 67 :149-159.
58. Petit I, Kravitz MS, Nagler A, et al. G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and upregulating CXCR4. Nature Immunol. 2002; 3(5):687.
59. Levesque LJ ,Bendall J ,Hendy B ,et al. SDF-1 is inactivated by proteolytic cleavage in the bone marrow of mice mobilized by either G-CSF or cyclophosphamide. Blood. 2001; 98(4): 831.
60. Delgado M, Lewis IC, Loetscher P, et al. Rapid inactivation of stromal cell-derived factor-1 by cathepsin G associated with lymphocytes. Eur J Immunol. 2001; 31 (6): 699.
61. Levesque JP, Hendy J, Takamatsu Y, et al. Disruption of the CXCR4/CXCL12 chemotactic interaction during hematopoietic stem cell mobilization induced by G-CSF or cyclophosphamide. J Clin Invest. 2003; 111:187 – 196.
62. Voermans C , Kooi ML , Rodenhui S ,et al. In vitro migratory capacity of CD34+cells is related to hematopoietic recovery after autologous stem cell transplantation. Blood. 2001; 97 (3):799.
63. Dabusti M, Lanza F, Campioni D, et al. CXCR-4 expression on bone marrow CD34+cells prior to mobilization can predict mobilization adequacy in patients with hematologic malignancies. Hematol Stem Cell Res. 2003; 12(4):425-434.
64. Hattori K, Heissig B, Tashiro K, et al. Plasma elevation of stromal cell-derived factor-1 induces mobilization of mature and immature hematopoietic progenitor and stem cells. Blood. 2001; 97:3354-3360.
65. Perez LE, Alpdogan O, Shieh JH, et al. Increased plasma levels of stromal-derived factor-1 (SDF-1/CXCL12) enhance human thrombopoiesis and mobilize human colony-forming cells (CFC) in NOD/SCID mice. Exp Hematol. 2004 Mar; 32(3):300-7.
66. Pelus LM, Bian H, Fukuda S, et al. The CXCR4 agonist peptide, CTCE-0021, rapidly mobilizes polymorphonuclear neutrophils and hematopoietic progenitor cells into peripheral blood and synergizes with granulocyte colony-stimulating factor. Exp Hematol. 2005 Mar; 33(3):295-307.
67. Sweeney EA, Lortat-Jacob H, Priestley GV, et al. Sulfated polysaccharides increase plasma levels of SDF-1 in monkeys and mice: involvement in mobilization of stem/progenitor cells. Blood. 2002 Jan 1; 99(1):44-51.
68. Togel F, Isaac J, Hu Z, Weiss K, Westenfelder C. Renal SDF-1 signals mobilization and homing of CXCR4-positive cells to the kidney after ischemic injury. Kidney Int.2005 May;67(5):1772-84.
69. Moore M.A, Hattori K, Heissig B, et al. Mobilization of endothelial and hematopoietic stem and progenitor cells by adenovector-mediated elevation of serum levels of SDF-1, VEGF, and angiopoietin-1, Ann N Y Acad Sci. 2001; 938: 36–45.
70. Hiasa K, Ishibashi M, Ohtani K, et al. Gene transfer of stromal cell-derived factor-1alpha enhances ischemic vasculogenesis and angiogenesis via vascular endothelial growth factor/endothelial nitric oxide synthase-related pathway: next-generation chemokine therapy for therapeutic neovascularization, Circulation.2004; 109: 2454–61.
71. De Falco E, Porcelli D, Torella AR, et al. SDF-1 involvement in endothelial phenotype and ischemia-induced recruitment of bone marrow progenitor cells. Blood. 2004; 104: 3472-82.
72. Mohle R, Bautz F, Shalhin R, et al. The chemokine receptor CXCR4 is expressed on CD34+ hematopoietic progenitor and leukemia cells and mediates transendothelial migration induced by stromal cell-derivedfactor-1.Blood. 1998; 91 (12) :4523 - 4530.
73. Aiuti A, Webb IJ, Bleul C, et al. The chemokine SDF-1 is a chemoattractant for human CD34+ hematopoietic progenitor cells and provides a new mechanism to explain the mobilization of CD34+ progenitors to peripheria blood. J Exp Med. 1997; 185 (1):111 - 120.
74. Yamaguchi J, Kusano KF, Masuo O, et al. Stromal cell-derived factor-1 effects on ex vivo expanded endothelial progenitor cells recruitment for ischemic neovascularization. Circulation. 2003; 107:1322-1328.
75. Naiyer JA, Jo DY, Ahn J, et al. Stromal derived fator-1-induced chemokinesis of cord blood CD34 ( + ) cells (long-term culture-initiating cells) through endothelial cells is mediated by E-selectin. Blood. 1999; 94 (12):4011.
76. Voermans C ,Rood PML ,Hordijk PL ,et al. Adhesion molecules involved in transendothelial migration of human hematopoietic progenitor cells. Stem Cells. 2000; 18 (6):435.
77. Peled A, Kollet O, Ponomaryov T, et al. The chemokine SDF-1 activates the intrgrins L FA-1 ,VLA-4 and VLA-5 on immature human CD34 ( + ) cells: role in transendothelial/ stromal migration and engraftment of NOD/ SCID mice. Blood. 2000;95 (11) : 3289-3296.
78. Campbell JJ, Hedrick J, Zlotnik A, et al.Chemokines and the Arrest of Lymphocytes Rolling Under Flow Conditions, Scince 1998;279:381-384.
79. Peled A, Grabovsky V, Habler L, et al. The chemokine SDF-1 stimulates integrin-mediated arrest of CD34 ( + ) cells on vascular endothelium under shear flow. J Clin Invest. 1999; 104 (9) :1199.
80. Peled A, Petit I, Kollet O, et al. Dependence of human stem cell engraftment and repopulation of NOD/ SCID mice on CXCR4. Science. 1999; 283 (5403):845 - 848.
81. Kim CH, Broxmeyer HJ. In vitro behavior of hematopoietic progenitor cells under the influence of chemoattractants: stromal cell-derived factor-1, steel factor, and the bone marrow enviroment. Blood. 1998; 91(1):100 - 110.
82. Hernandez-Lopez C, Varas A, Sacedon R, et a1. Stromal cell-derived factor-1/CXCR4 signaling is critical for early human T-celldevelopment. Blood. 2002; 99(2):546-554.
83. Lataillade JJ, Clay D, Dupuy C, Rigal S, Jasmin C, Bourin P, et al. Chemokine SDF-1 enhances circulating CD34+ cell proliferation in synergy with cytokines: possible role in progenitor survival. Blood. 2000;95:756-68.
84. Hwang JH, Kim SW, Park SE, Yun HJ, Lee Y, Kim S, Jo DY. Overexpression of stromal cell-derived factor-1 enhances endothelium-supported transmigration, maintenance, and proliferation of hematopoietic progenitor cells. Stem Cells Dev. 2006 Apr;15(2):260-8.
85. Gong X, He X, Qi L, Zuo H, Xie Z. Stromal cell derived factor-1 acutely promotes neural progenitor cell proliferation in vitro by a mechanism involving the ERK1/2 and PI-3K signal pathways. Cell Biol Int. 2006 May;30(5):466-71.
86. Broxmeyer HE, Cooper S, Hangoc G, Kim CH. Stromal cell-derived factor-1/CXCL12 selectively counteracts inhibitory effects of myelosuppressive chemokines on hematopoietic progenitor cell proliferation in vitro. Stem Cells Dev. 2005 Apr;14(2):199-203.
87. Lataillade JJ, Domenech J, Le Bousse-Kerdiles MC. Stromal cell-derived factor-1 (SDF-1)\CXCR4 couple plays multiple roles on haematopoietic progenitors at the border between the old cytokine and new chemokine worlds: survival, cell cycling and trafficking. Eur Cytokine Netw. 2004;15:177-88.
88. Lataillade JJ, Clay D, Bourin P, et al. Stromal cell-derived factor 1 regulates primitive hematopoiesis by suppressing apoptosis and by promoting G(0)/G(1) transition in CD34(+) cells: evidence for an autocrine/paracrine mechanism. Blood. 2002; 99: 1117-29.
89. Tan Y, Shao H, Eton D, Yang Z, Alonso-Diaz L, Zhang H, Schulick A, Livingstone AS, Yu H.Stromal cell-derived factor-1 enhances pro-angiogenic effect of granulocyte-colony stimulating factor. Cardiovasc Res. 2007 Mar 1;73(4):823-32.
90. Askari AT, Unzek S, Popovic ZB, et a1. Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic eardiomyopathy. Lancet. 2003; 362(9385): 697-703.
91. Abbott JD, Huang Y, Liu D, et a1. Stromal cell-derived factor-1 alpha plays a critical role in stem cell recruitment to the heart after myocardial infarction but is not suficientto induce homing in the absence of injury. Circulation. 2004; 110(21): 3300-3305.
92. Ma N, Stamm C, Kaminski A, et a1. Human cord blood cells induce angiogenesis following myocardial infarction in NOD/scid-mice. Cardiovasc Res. 2005; 66(1): 45-54.
93. Wang Y, Haider HKh, Ahmad N, Zhang D, Ashraf M. Evidence for ischemia induced host-derived bone marrow cell mobilization into cardiac allografts. J Mol Cell Cardiol. 2006 Sep; 41(3):478-87.
94. Woo YJ, Grand TJ, Berry MF, Atluri P, Moise MA, Hsu VM, Cohen J, Fisher O, Burdick J, Taylor M, Zentko S, Liao G, Smith M, Kolakowski S, Jayasankar V, Gardner TJ, Sweeney HL. Stromal cell-derived factor and granulocyte-monocyte colony-stimulating factor form a combined neovasculogenic therapy for ischemic cardiomyopathy. J Thorac Cardiovasc Surg. 2005 Aug;130(2):321-9.
95. Tang YL, Qian K, Zhang YC, Shen L, Phillips MI. Mobilizing of haematopoietic stem cells to ischemic myocardium by plasmid mediated stromal-cell-derived factor-1alpha (SDF-1alpha) treatment. Regul Pept. 2005 Feb 15;125(1-3):1-8.
96. Zhang G, Nakamura Y, Wang X, Hu Q, Suggs LJ, Zhang J.Controlled Release of Stromal Cell-Derived Factor-1alpha In situ Increases C-kit+ Cell Homing to the Infarcted Heart. Tissue Eng. 2007 Feb 22; [Epub ahead of print]
97. Miller JT, Bartley JH, Wimborne HJ, Walker AL, Hess DC, Hill WD, Carroll JE. The neuroblast and angioblast chemotaxic factor SDF-1 (CXCL12) expression is briefly up regulated by reactive astrocytes in brain following neonatal hypoxic-ischemic injury. BMC Neurosci. 2005 Oct 31;6:63.
98. Hill WD, Hess DC, Martin-Studdard A, Carothers JJ, Zheng J, Hale D, Maeda M, Fagan SC, Carroll JE, Conway SJ. SDF-1 (CXCL12) is upregulated in the ischemic penumbra following stroke: association with bone marrow cell homing to injury. J Neuropathol Exp Neurol. 2004 Jan;63(1):84-96
2. Bennett MR. In-stent stenosis: pathology and implications for the development of drug eluting stents. Heart. 2003 Feb;89(2):218-24.
3. Rigattieri S, Patrizi R, Silvestri P, Di Russo C, Musto C, Ferraiuolo G, et al. Very late thrombosis of a drug-eluting stent deployed during primary angioplasty for ST-elevation myocardial infarction. J Cardiovasc Med (Hagerstown). 2006 Oct;7(10):771-774.
4. El-Bialy A, Shenoda M, Caraang C. Refractory coronary vasospasm following drug-eluting stent placement treated with cyproheptadine. J Invasive Cardiol. 2006 Feb;18(2):E95-8.
5. Slavin L, Chhabra A, Tobis JM. Drug-eluting stents: preventing restenosis. Cardiol Rev. 2007 Jan-Feb;15(1):1-12.
6. Ligthart S, Vlemmix F, Dendukuri N, Brophy JM. The cost-effectiveness of drug-eluting stents: a systematic review. CMAJ. 2007 Jan 16; 176(2):199-205.
7. Skyttberg N, Linder R, Carlsson J. Drug-eluting stents can increase the risk of late stent thrombosis. Lakartidningen. 2006 Sep 27-Oct 3; 103(39):2845-7.
8. Movahed MR, Vu J, Ahsan C. Simultaneous subacute stent thrombosis of two drug-eluting stents in the left anterior descending and the circumflex coronary arteries. Case report and review of the literature. J Invasive Cardiol. 2006 Jul; 18(7):E198-202.
9. Feres F, Costa JR Jr, Abizaid A. Very late thrombosis after drug-eluting stents. Catheter Cardiovasc Interv. 2006 Jul; 68(1):83-8.
10. Li Y, Fukuda N, Kunimoto S, Yokoyama S, Hagikura K, Kawano T, Takayama T, Honye J, Kobayashi N, Mugishima H, Saito S, Serie K. Stent-based delivery of antisense oligodeoxynucleotides targeted to the PDGF A-chain decreases in-stent restenosis of the coronary artery. J Cardiovasc Pharmacol. 2006 Oct;48(4):184-90.
11. Kappert K, Sparwel J, Sandin A, Seiler A, Siebolts U, Leppanen O, Rosenkranz S, Ostman A. Antioxidants relieve phosphatase inhibition and reduce PDGF signaling incultured VSMCs and in restenosis. Arterioscler Thromb Vasc Biol. 2006 Dec;26(12):2644-51.
12. Levitzki A. PDGF receptor kinase inhibitors for the treatment of restenosis. Cardiovasc Res. 2005 Feb 15;65(3):581-6.
13. Serruys PW, Heyndrickx GR, Patel J, Cummins PA, Kleijne JA, Clowes AW. Effect of an anti-PDGF-beta-receptor-blocking antibody on restenosis in patients undergoing elective stent placement. Int J Cardiovasc Intervent. 2003;5(4):214-22.
14. Post MJ, Laham RJ, Kuntz RE, Novicki D, Simons M. The effect of intracoronary fibroblast growth factor-2 on restenosis after primary angioplasty or stent placement in a pig model of atherosclerosis. Clin Cardiol. 2002 Jun;25(6):271-8.
15. Chang Y, Ceacareanu B, Zhuang D, Zhang C, Pu Q, Ceacareanu AC, Hassid A. Counter-regulatory function of protein tyrosine phosphatase 1B in platelet-derived growth factor- or fibroblast growth factor-induced motility and proliferation of cultured smooth muscle cells and in neointima formation. Arterioscler Thromb Vasc Biol. 2006 Mar; 26(3): 501-7.
16. Camozzi M, Zacchigna S, Rusnati M, Coltrini D, Ramirez-Correa G, Bottazzi B, Mantovani A, Giacca M, Presta M. Pentraxin 3 inhibits fibroblast growth factor 2-dependent activation of smooth muscle cells in vitro and neointima formation in vivo. Arterioscler Thromb Vasc Biol. 2005 Sep;25(9):1837-42.
17. Otsuka G, Agah R, Frutkin AD, Wight TN, Dichek DA. Transforming growth factor beta 1 induces neointima formation through plasminogen activator inhibitor-1-dependent pathways. Arterioscler Thromb Vasc Biol. 2006 Apr;26(4):737-43.
18. Ando H, Fukuda N, Kotani M, Yokoyama S, Kunimoto S, Matsumoto K, Saito S, Kanmatsuse K, Mugishima H. Chimeric DNA-RNA hammerhead ribozyme targeting transforming growth factor-beta 1 mRNA inhibits neointima formation in rat carotid artery after balloon injury. Eur J Pharmacol. 2004 Jan 12;483(2-3):207-14.
19. Schober A, Knarren S, Lietz M, Lin EA, Weber C. Crucial role of stromal cell-derived factor-1alpha in neointima formation after vascular injury in apolipoprotein E-deficient mice. Circulation. 2003; 108(20):2491-2497.
20. Zernecke A, Schober A, Bot I, von Hundelshausen P, Liehn EA, Mopps B, et al.SDF-1alpha/CXCR4 axis is instrumental in neointimal hyperplasia and recruitment of smooth muscle progenitor cells. Circ Res. 2005; 96(7):784-791.
21. Liuzzo JP, Ambrose JA, Coppola JT. Sirolimus- and taxol-eluting stents differ towards intimal hyperplasia and re-endothelialization. J Invasive Cardiol. 2005 Sep;17(9):497-502.
22. Behrendt D, Ganz P. Endothelial function: from vascular biology to clinical applications. Am J Cardiol. 2002; 90 (suppl): 40L-48L.
23. Pauleto P, Sartore S, Pessina AC. Smooth muscle-cell proliferation and differentiation in neointima formation and vascular restenosis. Clin Sci. 1994; 87: 467-479.
24. Urao N, Okigaki M, Yamada H, Aadachi Y, Matsuno K, Matsui A, Matsunaga S, Tateishi K, Nomura T, Takahashi T, Tatsumi T, Matsubara H. Erythropoietin-mobilized endothelial progenitors enhance reendothelialization via Akt-endothelial nitric oxide synthase activation and prevent neointimal hyperplasia. Circ Res. 2006 Jun 9;98(11):1405-13.
25. Iwakura A, Luedemann C, Shastry S, Hanley A, Kearney M, Aikawa R, Isner JM, Asahara T, Losordo DW. Estrogen-mediated, endothelial nitric oxide synthase-dependent mobilization of bone marrow-derived endothelial progenitor cells contributes to reendothelialization after arterial injury. Circulation. 2003 Dec 23;108(25):3115-21.
26. Shariat-Madar Z, Mahdi F, Warnock M, Homeister JW, Srikanth S, Krijanovski Y, Murphey LJ, Jaffa AA, Schmaier AH.Bradykinin B2 receptor knockout mice are protected from thrombosis by increased nitric oxide and prostacyclin. Blood. 2006 Jul 1;108(1):192-9.
27. Hu H, Zhang XX, Wang YY, Chen SZ.Honokiol inhibits arterial thrombosis through endothelial cell protection and stimulation of prostacyclin. Acta Pharmacol Sin. 2005 Sep;26(9):1063-8.
28. Iwakura A, Shastry S, Luedemann C, et al. Estradiol enhances recovery after myocardial infarction by augmenting incorporation of bone marrow-derived endothelial progenitor cells into sites of ischemia-induced neovascularization via endothelial nitric oxide synthase-mediated activation of matrix metalloproteinase-9. Circulation. 2006;113:1605-14.
29. Ishizawa K, Kubo H, Yamada M, et al. Hepatocyte growth factor induces angiogenesis in injured lungs through mobilizing endothelial progenitor cells. Biochem Biophys Res Commun. 2004;324:276-80.
30. Tepper OM, Capla JM, Galiano RD, et al. Adult vasculogenesis occurs through in situ recruitment, proliferation, and tubulization of circulating bone marrow-derived cells. Blood. 2005;105:1068-77.
31. Walter DH, Rittig K, Bahlmann FH, et al. Statin therapy accelerate reendothelialization: a novel effect involving mobilization and incorporation of bone marrow-derived endothelial progenitor cells. Circulation 2002; 105: 3017-24.
32. He T, Smith LA, Harrington S, et al. Transplantation of circulating endothelial progenitor cells restores endothelial function of denuded rabbit carotid arteries. Stroke. 2004;35:2378-84.
33. Werner N, Junk S, Laufs U, et al. Intravenous transfusion of endothelial progenitor cells reduces neointima formation after vascular injury. Circ Res. 2003;93:e17-24.
34. J G, Cq W, Hh F, Hy D, Xl X, Ym X, et al. Effects of resveratrol on endothelial progenitor cells and their contributions to reendothelialization in intima-injured rats. J Cardiovasc Pharmacol. 2006 May;47(5):711-21.
35. Walter DH, Rittig K, Bahlmann FH, Kirchmair R, Silver M, Murayama T, et al. Statin therapy accelerate reendothelialization: a novel effect involving mobilization and incorporation of bone marrow-derived endothelial progenitor cells. Circulation. 2002; 105: 3017-24.
36. Natori T, Sata M, Washida M, Hirata Y, Nagai R, Makuuchi M. G-CSF stimulates angiogenesis and promotes tumor growth: potential contribution of bone marrow-derived endothelial progenitor cells. Biochem Biophys Res Commun. 2002 Oct 4;297(4):1058-61.
37. De Falco E, Porcelli D, Torella AR, et al. SDF-1 involvement in endothelial phenotype and ischemia-induced recruitment of bone marrow progenitor cells. Blood. 2004; 104: 3472-82.
38. Bonello L, Basire A, Sabatier F, Paganelli F, Dignat-George F. Endothelial injury induced by coronary angioplasty triggers mobilization of endothelial progenitor cells in patients with stable coronary artery disease. J Thromb Haemost. 2006May;4(5):979-81.
39. Gill M, Dias S, Hattori K, Rivera ML, Hicklin D, Witte L, et al. Vascular trauma induces rapid but transient mobilization of VEGFR2(+)AC133(+) endothelial precursor cells. Circ Res. 2001 Feb 2;88(2):167-74.
40. Scheubel RJ, Zorn H, Silber RE, Kuss O, Morawietz H, Holtz J, et al. Age-dependent depression in circulating endothelial progenitor cells in patients undergoing coronary artery bypass grafting. J Am Coll Cardiol. 2003 Dec 17;42(12):2073-80.
41. Yang Z, Wang JM, Chen L, Luo CF, Tang AL, Tao J. Acute exercise-induced nitric oxide production contributes to upregulation of circulating endothelial progenitor cells in healthy subjects. J Hum Hypertens. 2007 Mar 8; [Epub ahead of print]
42. Wahl P, Bloch W, Schmidt A. Exercise has a Positive Effect on Endothelial Progenitor Cells, which Could be Necessary for Vascular Adaptation Processes. Int J Sports Med. 2006 Nov 16; [Epub ahead of print]
43. Laufs U, Urhausen A, Werner N, Scharhag J, Heitz A, Kissner G, Bohm M, Kindermann W, Nickenig G. Running exercise of different duration and intensity: effect on endothelial progenitor cells in healthy subjects. Eur J Cardiovasc Prev Rehabil. 2005 Aug;12(4):407-14.
44. He T, Smith LA, Harrington S, Nath KA, Caplice NM, Katusic ZS. Transplantation of circulating endothelial progenitor cells restores endothelial function of denuded rabbit carotid arteries. Stroke. 2004;35:2378-84.
45. Griese DP, Ehsan A, Melo LG, Kong D, Zhang L, Mann MJ, , et al. Isolation and Transplantation of Autologous Circulating Endothelial Cells Into Denuded Vessels and Prosthetic Grafts. Circulation. 2003;108:2710.
46. Wassmann S, Werner N, Czech T, Nickenig G. Improvement of endothelial function by systemic transfusion of vascular progenitor cells. Circ Res. 2006 Oct 13;99(8):e74-83.
47. Yamaguchi J, Kusano KF, Masuo O, et al. Stromal cell-derived factor-1 effects on ex vivo expanded endothelial progenitor cells recruitment for ischemic neovascularization. Circulation. 2003; 107:1322-1328.
48. Hiasa K, Ishibashi M, Ohtani K, et al. Gene transfer of stromal cell-derived factor-1alpha enhances ischemic vasculogenesis and angiogenesis via vascular endothelial growth factor/endothelial nitric oxide synthase-related pathway:next-generation chemokine therapy for therapeutic neovascularization. Circulation.2004; 109: 2454–61.
49. Moore M.A, Hattori K, Heissig B, et al. Mobilization of endothelial and hematopoietic stem and progenitor cells by adenovector-mediated elevation of serum levels of SDF-1, VEGF, and angiopoietin-1, Ann N Y Acad Sci. 2001; 938: 36–45.
50. Aiuti A, Turchetto L, Cota M, et al. Human CD34+ cells express CXCR4 and its ligand stromal cell-derived factor-1. Implications for infection by T-cell tropic human immunodeficiency virus. Blood. 1999;94:62-73.
51. Walter DH, Haendeler J, Reinhold J, Rochwalsky U, Seeger F, Honold J, Hoffmann J, Urbich C, Lehmann R, Arenzana-Seisdesdos F, Aicher A, Heeschen C, Fichtlscherer S, Zeiher AM, Dimmeler S. Impaired CXCR4 signaling contributes to the reduced neovascularization capacity of endothelial progenitor cells from patients with coronary artery disease. Circ Res. 2005 Nov 25;97(11):1142-51.
52. Smadja DM, Bieche I, Uzan G, Bompais H, Muller L, Boisson-Vidal C, Vidaud M, Aiach M, Gaussem P. PAR-1 activation on human late endothelial progenitor cells enhances angiogenesis in vitro with upregulation of the SDF-1/CXCR4 system. Arterioscler Thromb Vasc Biol. 2005 Nov;25(11):2321-7.
53. Lataillade JJ, Domenech J, Le Bousse-Kerdiles MC. Stromal cell-derived factor-1 (SDF-1)\CXCR4 couple plays multiple roles on haematopoietic progenitors at the border between the old cytokine and new chemokine worlds: survival, cell cycling and trafficking. Eur Cytokine Netw. 2004;15:177-88.
54. Frenette PS, Weiss L. Sulfated glycans induce rapid hematopoietic progenitor cell mobilization:evidence for selectin dependent and independent mechanisms. Blood. 2000; 96 (7) :2460.
55. Hattori K, Heissig B , Tashiro K, et al. Plasma elevation of stromal cell-derived factor-1 induces mobilization of mature and immature hematopoietic progenitor and stem cells. Blood. 2001; 97 :3354 - 3360.
56. Kalka C, Masuda H, Takahashi T, et al. Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. Proc Natl Acad Sci USA. 2000; 97: 3422-7.
57. Vasa M, Fichtlscherer S, Aicher A, et al. Number and migratory activity of circulatingendothelial progenitor cells inversely correlate with risk factors for coronary artery disease. Circ Res. 2001; 89: E1-7.
58. Gensch C, Clever Y, Werner C, Hanhoun M, Bohm M, Laufs U.Regulation of endothelial progenitor cells by prostaglandin E1 via inhibition of apoptosis. J Mol Cell Cardiol. 2007 Mar; 42(3):670-7.
59. Gensch C, Clever YP, Werner C, Hanhoun M, Bohm M, Laufs U.The PPAR-gamma agonist pioglitazone increases neoangiogenesis and prevents apoptosis of endothelial progenitor cells. Atherosclerosis. 2006 Jul 27; [Epub ahead of print]
60. Hill JM, Zalos G, Halcox JP, et al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med. 2003; 348: 593-600.
61. Schmidt-Lucke C, Rossig L, Fichtlscherer S, et al. Reduced number of circulating endothelial progenitor cells predicts future cardiovascular events: proof of concept for the clinical importance of endogenous vascular repair. Circulation. 2005;111:2981-7.
62. 崔斌 黄岚 宋耀明 李爱民 晋军 覃军 于学军 耿召华。冠心病患者循环内皮祖细胞 与 相 关 危 险 因 素 及 冠 状 动 脉 病 变 的 关 系 。 中 华 心 血 管 病 杂 志 。2006;33(9):785-788。
63. Valgimigli M, Rigolin GM, Fucili A, et al. CD34+ and endothelial progenitor cells in patients with various degrees of congestive heart failure. Circulation. 2004;110:1209-12.
64. Edelberg JM, Tang L, Hattori K, et al. Young adult bone marrow-derived endothelial precursor cells restore aging-impaired cardiac angiogenic function. Circ Res. 2002;90:E89-93.
65. Yamamoto K, Kondo T, Suzuki S, et al. Molecular evaluation of endothelial progenitor cells in patients with ischemic limbs: therapeutic effect by stem cell transplantation. Arterioscler Thromb Vasc Biol. 2004;24:e192-6.
66. Deb A, Wang SH, Skelding K, et al. Bone marrow-derived myofibroblasts are present in adult human heart valves. J Heart Valve Dis. 2005;14:674-8.
67. Nagasawa T, Kikutani H, Kishimoto T. Molecular cloning and structure of a pre-B-cell-growth stimulating factor. Proc Natl Acad Sci U S A. 1994;91:2305-9.
68. Kozuka T, Ishimaru F, Fujii K, Masuda K, Kaneda K, Imai T, Fujii N, Ishikura H, Hongo S, Watanabe T, Shinagawa K, Ikeda K, Niiya K, Harada M, TanimotoM.Plasma stromal cell-derived factor-1 during granulocyte colony-stimulating factor-induced peripheral blood stem cell mobilization. Bone Marrow Transplant. 2003 Apr;31(8):651-4.
69. Hattori K, Heissig B, Tashiro K, Honjo T, Tateno M, Shieh JH, Hackett NR, Quitoriano MS, Crystal RG, Rafii S, Moore MA.Plasma elevation of stromal cell-derived factor-1 induces mobilization of mature and immature hematopoietic progenitor and stem cells. Blood. 2001 Jun 1;97(11):3354-60.
70. Lataillade JJ, Clay D, Dupuy C, Rigal S, Jasmin C, Bourin P, et al. Chemokine SDF-1 enhances circulating CD34+ cell proliferation in synergy with cytokines: possible role in progenitor survival. Blood. 2000;95:756-68.
71. Gotoh A, Miyazawa K, Yaguchi M, Broxmeyer H. Priming with SDF-1 induces enhancement of cytokine-dependent survival effect and pronounced activation of MAP kinase signaling in hematopoietic cells. Blood. 1998;92:200a.
72. Burger JA, Tsukada N, Burger M, Zvaifler NJ, Dell'Aquila M, Kipps T. Blood-derived nurse-like cells protect chronic lymphocytic leukemia B cells from spontaneous apoptosis through stromal cell-derived factor-1. Blood. 2000;96:2655-63.
73. Kollet O, Grabovsky V, Franitza S, Lider O, Alon R, Lapidot T. SDF-1 induces survival, adhesion, and migration in 3D ECM like gels of murine CXCR-4null fetal liver cells via another GPCR . Blood. 2000;96:65a.
74. 陈剑飞, 黄岚, 晋军 武晓静 刘兰 周健 赵晓晖 崔斌。年龄对大鼠骨髓内皮祖细胞数量和功能的影响及其意义。中华心血管病杂志。2006;34(11):1026-8.
75. Hamada H, Kim MK, Iwakura A, Ii M, Thorne T, Qin G, Asai J, Tsutsumi Y, Sekiguchi H, Silver M, Wecker A, Bord E, Zhu Y, Kishore R, Losordo DW. Estrogen receptors alpha and beta mediate contribution of bone marrow-derived endothelial progenitor cells to functional recovery after myocardial infarction. Circulation. 2006 Nov 21;114(21):2261-70.
76. Ohta T, Kikuta K, Imamura H, Takagi Y, Nishimura M, Arakawa Y, Hashimoto N, Nozaki K. Administration of ex vivo-expanded bone marrow-derived endothelial progenitor cells attenuates focal cerebral ischemia-reperfusion injury in rats. Neurosurgery. 2006 Sep; 59(3):679-86.
77. Strehlow K, Werner N, Berweiler J, Link A, Dirnagl U, Priller J, et al. Estrogenincreases bone marrow–derived endothelial progenitor cell production and diminishes neointima formation. Circulation. 2003;107:3059-3065.
78. Zhao YD, Courtman DW, Deng Y, Kugathasan L, Zhang Q, Stewart DJ. Rescue of monocrotaline-induced pulmonary arterial hypertension using bone marrow-derived endothelial-like progenitor cells: efficacy of combined cell and eNOS gene therapy in established disease. Circ Res. 2005 Mar 4;96(4):442-50.
79. Kong D, Melo LG, Mangi AA, Zhang L, Lopez-Ilasaca M, Perrella MA, et al. Enhanced inhibition of neointimal hyperplasia by genetically engineered endothelial progenitor cells. Circulation. 2004;109:1769-1775.
80. Dimmeler S, Aicher A, Vasa M, Mildner-Rihm C, Adler K, Tiemann M, et al. HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI 3-kinase/Akt pathway. J Clin Invest. 2001; 108(3):391-397.
81. Hyun-Jai C, Hyo-Soo K, Myoung-Mook L, Dae-Hee K, Hyun-Ju Y, Jin H, et al. Mobilized endothelial progenitor cells by granulocyte-macrophage colony-stimulating factor accelerate reendothelialization and reduce vascular inflammation after intravascular radiation. Circulation. 2003;108:2918.
82. Jin H, Chang-Hwan Y, Hyo-Soo K, Jin-Ho C, Hyun-Jae K, Kyung-Kook H, et al. Characterization of two types of endothelial progenitor cells and their different contributions to neovasculogenesis. ATVB. 2004;24:288.
83. Jun-Hui Z, Qian-Min T, Jun-Zhu C, Xing-Xiang W, Jian-Hua Z, Yun-Peng S, et al. Statins contribute to enhancement of the number and the function of endothelial progenitor cells from peripheral blood. Acta Physiologica Sinica. 2004;56(3):357-364.
84. Jun-hui Z, Xing-xiang W, Jun-zhu C, Yun-peng S, Jian-hua Z, Xiao-gang G, et al. Effects of puerarin on number and activity of endothelial progenitor cells from peripheral blood. Acta Pharmacologica Sinica. 2004;25(8):1045-1051.
85. Zemani F, Benisvy D, Galy-Fauroux I, Lokajczyk A, Colliec-Jouault S, Uzan G, et al. Low-molecular-weight fucoidan enhances the proangiogenic phenotype of endothelial progenitor cells. Biochemical Pharmacology. 2005;70(8) :1167-1175.
86. Jun Zhu C, Fu Rong Z, Qian Min T, Xing Xiang W, Jian Hua Z,Jun Hui Z. Number and activity of endothelial progenitor cells from peripheral blood in patients with hypercholesterolaemia. Clinical Science. 2004;107, 273–280.
87. Verma S, Kuliszewski MA, Shu-Hong L, Szmitko PE, Zucco L, Chao-Hung W, et al. C-Reactive Protein Attenuates Endothelial Progenitor Cell Survival, Differentiation, and Function. Circulation. 2004;109:2058-2067.
88. Zhou B, Cao XC, Fang ZH, Zheng CL, Han ZB, Ren H, Poon MC, Han ZC. Prevention of diabetic microangiopathy by prophylactic transplant of mobilized peripheral blood mononuclear cells. Acta Pharmacol Sin. 2007 Jan;28(1):89-97.
89. Sales VL, Engelmayr GC Jr, Mettler BA, Johnson JA Jr, Sacks MS, Mayer JE Jr. Transforming growth factor-beta1 modulates extracellular matrix production, proliferation, and apoptosis of endothelial progenitor cells in tissue-engineering scaffolds. Circulation. 2006 Jul 4;114(1 Suppl):I193-9.
90. Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenisis. Science. 1997;275:964-967.
91. 赵晓辉,黄岚,尹扬光,周健,方玉强,朱光旭,陈剑飞,崔斌。雌二醇对骨髓内皮祖细胞部分生物学功能的影响。中华老年心脑血管病杂志。2005; 8 (5):343-345。
92. Campbell JJ, Hedrick J, Zlotnik A, et al.Chemokines and the Arrest of Lymphocytes Rolling Under Flow Conditions, Scince. 1998;279:381-384.
93. Peled A, Grabovsky V, Habler L, et al. The chemokine SDF-1 stimulates integrin-mediated arrest of CD34 ( + ) cells on vascular endothelium under shear flow. J Clin Invest. 1999; 104 (9) :1199.
94. Peled A, Kollet O, Ponomaryov T, et al. The chemokine SDF-1 activates the integrins LFA-1, VLA-4, and VLA-5 on immature human CD34 + cells: role in transendothelial/stromal migration and engraftment of NOD/SCID mice. Blood. 2000; 95 :3289 – 3296.
95. Mohle R, Bautz F, Shalhin R, et al. The chemokine receptor CXCR4 is expressed on CD34+ hematopoietic progenitor and leukemia cells and mediates transendothelial migration induced by stromal cell-derivedfactor-1.Blood. 1998; 91 (12) :4523 - 4530.
96. Aiuti A, Webb IJ, Bleul C, et al. The chemokine SDF-1 is a chemoattractant for human CD34+hematopoietic progenitor cells and provides a new mechanism to explain the mobilization of CD34+ progenitors to peripheria blood. J Exp Med. 1997; 185 (1) :111 - 120.
97. Lataillade JJ, Clay D, Bourin P, et al. Stromal cell-derived factor 1 regulates primitive hematopoiesis by suppressing apoptosis and by promoting G(0)/G(1) transition in CD34(+) cells: evidence for an autocrine/paracrine mechanism. Blood. 2002; 99: 1117-29.
98. Lindner V, Fingerle J, Reidy MA. Mouse model of arterial injury. Circ Res. 1993; 73: 792–796.
99. Ma J, Ge J, Zhang S, Sun A, Shen J, Chen L, et al. Time course of myocardial stromal cell-derived factor 1 expression and beneficial effects of intravenously administered bone marrow stem cells in rats with experimental myocardial infarction. Basic Res Cardiol. 2005; 100: 217-223.
100. Abi-Younes S, Sauty A, Mach F, Sukhova GK, Libby P, Luster AD. The Stromal Cell–Derived Factor-1 Chemokine Is a Potent Platelet Agonist Highly Expressed in Atherosclerotic Plaques. Circulation Research. 2000;86:131.
101. Kim YS, Bigliani LU, Fujisawa M, Murakami K, Chang SS, Lee HJ, Lee FY, Blaine TA. Stromal cell-derived factor 1 (SDF-1, CXCL12) is increased in subacromial bursitis and downregulated by steroid and nonsteroidal anti-inflammatory agents. J Orthop Res. 2006 Aug; 24(8):1756-64.
102. Togel F, Isaac J, Hu Z, Weiss K, Westenfelder C. Renal SDF-1 signals mobilization and homing of CXCR4-positive cells to the kidney after ischemic injury. Kidney Int. 2005 May; 67(5):1772-84.
103. Werner N, Priller J, Laufs U, et al. Bone marrow-derived progenitor cells modulate vascular reendothelialization and neointimal formation: effect of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibition. Arterioscler. Thromb Vasc Biol. 2002; 22: 1567-72.
104. Papayannopoulou T, Current mechanistic scenarios in hematopoietic stem/progenitor cell mobilazation. Blood. 2004;103:1580-1585.
105. Vaday GG, Lider O. Extracellular matrix moieties , cytokines , and enzymes: dynamic effects on immune cell behavior and inflammation. J Leukoc Biol. 2000; 67 :149-159.
106. Petit I, Kravitz MS, Nagler A, et al. G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and upregulating CXCR4. Nature Immunol. 2002; 3 (5) :687.
107. Levesque LJ, Bendall J, Hendy B, et al. SDF-1 is inactivated by proteolytic cleavage in the bone marrow of mice mobilized by either G-CSF or cyclophosphamide. Blood. 2001; 98(4) : 831.
108. Delgado M, Lewis IC, Loetscher P, et al. Rapid inactivation of stromal cell-derived factor-1 by cathepsin G associated with lymphocytes. Eur J Immunol. 2001; 31 (6) :699.
109. Levesque JP, Hendy J, Takamatsu Y, et al. Disruption of the CXCR4/CXCL12 chemotactic interaction during hematopoietic stem cell mobilization induced by G-CSF or cyclophosphamide. J Clin Invest. 2003; 111 :187-196.
110. Voermans C, Kooi ML, Rodenhui S, et al. In vitro migratory capacity of CD34+cells is related to hematopoietic recovery after autologous stem cell transplantation. Blood. 2001; 97 (3) :799.
111. Dabusti M, Lanza F, Campioni D, et al. CXCR-4 expression on bone marrow CD34+cells prior to mobilization can predict mobilization adequacy in patients with hematologic malignancies. Hematol Stem Cell Res. 2003; 12(4) :425-434.
112. Perez LE, Alpdogan O, Shieh JH, et al.Increased plasma levels of stromal-derived factor-1 (SDF-1/CXCL12) enhance human thrombopoiesis and mobilize human colony-forming cells (CFC) in NOD/SCID mice. Exp Hematol. 2004 Mar;32(3):300-7.
113. Pelus LM, Bian H, Fukuda S, et al. The CXCR4 agonist peptide, CTCE-0021, rapidly mobilizes polymorphonuclear neutrophils and hematopoietic progenitor cells into peripheral blood and synergizes with granulocyte colony-stimulating factor. Exp Hematol. 2005 Mar;33(3):295-307.
114. Sweeney EA, Lortat-Jacob H, Priestley GV, et al. Sulfated polysaccharides increase plasma levels of SDF-1 in monkeys and mice: involvement in mobilization of stem/progenitor cells. Blood. 2002 Jan 1;99(1):44-51.
115. Nagano M, Yamashita T, Hamada H, Ohneda K, Kimura KI, Nakagawa T, Shibuya M, Yoshikawa H, Ohneda O. Identification of functional endothelial progenitor cells suitable for the treatment of ischemic tissue using human umbilical cord blood. Blood. 2007 Mar 22; [Epub ahead of print]
116. Lee SP, Youn SW, Cho HJ, Li L, Kim TY, Yook HS, Chung JW, Hur J, Yoon CH, Park KW, Oh BH, Park YB, Kim HS. Integrin-linked kinase, a hypoxia-responsivemolecule, controls postnatal vasculogenesis by recruitment of endothelial progenitor cells to ischemic tissue. Circulation. 2006 Jul 11;114(2):150-9.
117. Irie H, Tatsumi T, Takamiya M, Zen K, Takahashi T, Azuma A, Tateishi K, Nomura T, Hayashi H, Nakajima N, Okigaki M, Matsubara H. Carbon dioxide-rich water bathing enhances collateral blood flow in ischemic hindlimb via mobilization of endothelial progenitor cells and activation of NO-cGMP system. Circulation. 2005 Mar 29; 111(12): 1523-9.
118. Ii M, Nishimura H, Iwakura A, Wecker A, Eaton E, Asahara T, Losordo DW. Endothelial progenitor cells are rapidly recruited to myocardium and mediate protective effect of ischemic preconditioning via "imported" nitric oxide synthase activity. Circulation. 2005 Mar 8; 111(9): 1114-20.
119. Lapidot T, Kollet O. The essential roles of the chemokine SDF-1 and its receptor CXCR4 in human stem cell homing and repopulation of transplanted immune-deficient NOD/SCID and NOD/SCID/B2m(null) mice. Leukemia. 2002 Oct;16(10):1992-2003.
120. Peled A, Petit I, Kollet O, et al. Dependence of human stem cell engraftment and repopulation of NOD/ SCID mice on CXCR4. Science. 1999; 283 (5403):845 - 848.
121. Kim CH, Broxmeyer HJ. In vitro behavior of hematopoietic progenitor cells under the influence of chemoattractants: stromal cell-derived factor-1, steel factor, and the bone marrow enviroment. Blood. 1998; 91(1):100 - 110.
122. Tan Y, Shao H, Eton D, Yang Z, Alonso-Diaz L, Zhang H, Schulick A, Livingstone AS, Yu H.Stromal cell-derived factor-1 enhances pro-angiogenic effect of granulocyte-colony stimulating factor. Cardiovasc Res. 2007 Mar 1;73(4):823-32.
1. WHO. World Health Report [EB/OL]. [2003]. http://www.who.int/whr/en/.
2. AHA. Heart disease and stroke statistics-2004 update [EB/OL]. Dallas, Tex: American Heart Association, 2003.
3. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Lancet. 1988; 2:349.
4. Peters RJ, Mehta SR, Fox KA, et al. Effects of aspirin dose when used alone or in combination with clopidogrel in patients with acute coronary syndromes: Observations from the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) Study. Circulation. 2003;108:1682.
5. Freemantle N, Cleland J, Young P, et al. Beta blockade after myocardial infarction: Systematic review and meta regression analysis. BMJ. 1999; 318:1730.
6. Dargie HJ. Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: The CAPRICORN randomised trial. Lancet. 2001; 357:1385.
7. ACE Inhibitor Myocardial Infarction Collaborative Group. Indications for ACE inhibitors in the early treatment of acute myocardial infarction: Systematic overview of individual data from 100,000 patients in randomized trials. Circulation. 1998; 97:2202.
8. Pfeffer MA. ACE inhibitors in acute myocardial infarction: Patient selection and timing. Circulation. 1998; 97:2192.
9. Pitt B, Waters D, Brown WV, et al. Aggressive lipid-lowering therapy compared with angioplasty in stable coronary artery disease. Atorvastatin versus Revascularization Treatment Investigators. N Engl J Med. 1999; 341:70–76.
10. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: A randomised placebo-controlled trial. Lancet. 2002; 360:7–22.
11. Widimsky P, Budesinsky T, Vorac D, et al. Long distance transport for primary angioplasty vs immediate thrombolysis in acute myocardial infarction. Final results ofthe randomized national multicentre trial—PRAGUE-2. Eur Heart J. 2003; 24:94.
12. Grines CL, Westerhausen DR Jr, Grines LL, et al. A randomized trial of transfer for primary angioplasty versus on-site thrombolysis in patients with high-risk myocardial infarction: The Air Primary Angioplasty in Myocardial Infarction study. J Am Coll Cardiol. 2002; 39:1713.
13. Kober L, Torp-Pedersen C, Carlsen JE, et al. A clinical trial of the angiotensin-converting- enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. Trandolapril Cardiac Evaluation (TRACE) Study Group. N Engl J Med. 1995; 333:1670,
14. The SOLVD Investigators. Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. N Engl J Med. 1992; 327:685.
15. BEST Trial Investigators. A trial of the beta-adrenergic blocker bucindolol in patients with advanced heart failure. N Engl J Med. 2001; 344:1659.
16. Bristow MR. Anti-adrenergic therapy of chronic heart failure: Surprises and new opportunities. Circulation. 2003; 107:1100.
17. Pitt B. Aldosterone blockade in patients with systolic left ventricular dysfunction. Circulation. 2003; 108:1790.
18. Pitt B, Remme W, Zannad F, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003; 348:1309.
19. Caveliers V, De Keulenaer G, Everaert H, Van Riet I, Van Camp G, Verheye S, Roland J, Schoors D, Franken PR, Schots R. In vivo visualization of (111)In labeled CD133+ peripheral blood stem cells after intracoronary administration in patients with chronic ischemic heart disease. Q J Nucl Med Mol Imaging. 2007 Mar;51(1):61-6.
20. Kawamura A, Horie T, Tsuda I, Abe Y, Yamada M, Egawa H, Iida J, Sakata H, Onodera K, Tamaki T, Furui H, Kukita K, Meguro J, Yonekawa M, Tanaka S. Clinical study of therapeutic angiogenesis by autologous peripheral blood stem cell (PBSC) transplantation in 92 patients with critically ischemic limbs. J Artif Organs. 2006;9(4):226-33.
21. Chen S, Liu Z, Tian N, Zhang J, Yei F, Duan B, Zhu Z, Lin S, Kwan TW.Intracoronary transplantation of autologous bone marrow mesenchymal stem cells for ischemic cardiomyopathy due to isolated chronic occluded left anterior descending artery. J Invasive Cardiol. 2006 Nov;18(11):552-6.
22. Jiang W, Ma A, Wang T, Han K, Liu Y, Zhang Y, Dong A, Du Y, Huang X, Wang J, Lei X, Zheng X. Homing and differentiation of mesenchymal stem cells delivered intravenously to ischemic myocardium in vivo: a time-series study. Pflugers Arch. 2006 Oct;453(1):43-52.
23. Uemura R, Xu M, Ahmad N, Ashraf M. Bone marrow stem cells prevent left ventricular remodeling of ischemic heart through paracrine signaling. Circ Res. 2006 Jun 9;98(11):1414-21.
24. Krugliakov PV, Sokolova IB, Amineva KhK, Nekrasova NN, Viide SV, Cherednichenko NN, Zaritskii AIu, Semernin EN, Kisliakova TV, Polyntsev DG. Mesenchymal stem cell transplantation for myocardial reparation of rat experimental heart failure. Tsitologiia. 2004;46(12):1043-54.
25. Ozbaran M, Omay SB, Nalbantgil S, Kultursay H, Kumanlioglu K, Nart D, Pektok E. Autologous peripheral stem cell transplantation in patients with congestive heart failure due to ischemic heart disease. Eur J Cardiothorac Surg. 2004 Mar;25(3):342-50; discussion 350-1.
26. Belenkov IuN, Ageev FT, Mareev VIu, Savchenko VG. Mobilization of bone marrow stem cells in the management of patients with heart failure. Protocol and first results of ROT FRONT trial. Kardiologiia. 2003;43(3):7-12.
27. Urbanek K, Torella D, Sheikh F, De Angelis A, Nurzynska D, Silvestri F, Beltrami CA, Bussani R, Beltrami AP, Quaini F, Bolli R, Leri A, Kajstura J, Anversa P. Myocardial regeneration by activation of multipotent cardiac stem cells in ischemic heart failure. Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8692-7.
28. Kang HJ, Kim HS, Koo BK, Kim YJ, Lee D, Sohn DW, Oh BH, Park YB.Intracoronary infusion of the mobilized peripheral blood stem cell by G-CSF is better than mobilization alone by G-CSF for improvement of cardiac function and remodeling: 2-year follow-up results of the Myocardial Regeneration and Angiogenesis in Myocardial Infarction with G-CSF and Intra-Coronary Stem Cell Infusion (MAGIC Cell) 1 trial. Am Heart J. 2007 Feb;153(2): 237.e1-8.
29. Kastrup J, Ripa RS, Wang Y, Jorgensen E. Myocardial regeneration induced by granulocyte- colony-stimulating factor mobilization of stem cells in patients with acute or chronic ischaemic heart disease: a non-invasive alternative for clinical stem cell therapy? Eur Heart J. 2006 Dec;27(23):2748-54.
30. Ripa RS, Jorgensen E, Wang Y, Thune JJ, Nilsson JC, Sondergaard L, Johnsen HE, Kober L, Grande P, Kastrup J. Stem cell mobilization induced by subcutaneous granulocyte-colony stimulating factor to improve cardiac regeneration after acute ST-elevation myocardial infarction: result of the double-blind, randomized, placebo-controlled stem cells in myocardial infarction (STEMMI) trial. Circulation. 2006 Apr 25;113(16):1983-92.
31. Pompilio G, Cannata A, Peccatori F, Bertolini F, Nascimbene A, Capogrossi MC, Biglioli P. Autologous peripheral blood stem cell transplantation for myocardial regeneration: a novel strategy for cell collection and surgical injection. Ann Thorac Surg. 2004 Nov;78(5):1808-12.
32. Lee SP, Youn SW, Cho HJ, Li L, Kim TY, Yook HS, Chung JW, Hur J, Yoon CH, Park KW, Oh BH, Park YB, Kim HS. Integrin-linked kinase, a hypoxia-responsive molecule, controls postnatal vasculogenesis by recruitment of endothelial progenitor cells to ischemic tissue. Circulation. 2006 Jul 11;114(2):150-9.
33. Yoon CH, Hur J, Oh IY, Park KW, Kim TY, Shin JH, Kim JH, Lee CS, Chung JK, Park YB, Kim HS. Intercellular adhesion molecule-1 is upregulated in ischemic muscle, which mediates trafficking of endothelial progenitor cells. Arterioscler Thromb Vasc Biol. 2006 May;26(5): 1066-72.
34. Fan CL, Gao PJ, Che ZQ, Liu JJ, Wei J, Zhu DL.Therapeutic neovascularization by autologous transplantation with expanded endothelial progenitor cells from peripheral blood into ischemic hind limbs. Acta Pharmacol Sin. 2005 Sep;26(9):1069-75.
35. Ii M, Nishimura H, Iwakura A, Wecker A, Eaton E, Asahara T, Losordo DW.Endothelial progenitor cells are rapidly recruited to myocardium and mediate protective effect of ischemic preconditioning via "imported" nitric oxide synthase activity. Circulation. 2005 Mar 8;111(9):1114-20.
36. Yi C, Xia W, Zheng Y, Zhang L, Shu M, Liang J, Han Y, Guo S.Transplantation of endothelial progenitor cells transferred by vascular endothelial growth factor gene for vascular regeneration of ischemic flaps. J Surg Res. 2006 Sep;135(1):100-6.
37. Nagasawa T, Kikutani H, Kishimoto T. Molecular cloning and structure of a pre-B cell growth-stimulating factor. Proc Natl Acad Sci USA. 1994; 91: 2305 – 2309.
38. Psenak O. Stromal cell-derived factor-1(SDF-1). Its structure and function. Cas Lek Cesk. 2001; 140(12):355-363.
39. Schober A, Knarren S, Lietz M, Lin EA, Weber C. Crucial role of stromal cell-derived factor-1alpha in neointima formation after vascular injury in apolipoprotein E-deficient mice. Circulation. 2003 Nov 18; 108(20):2491-7.
40. Zernecke A, Schober A, Bot I, von Hundelshausen P, Liehn EA, Mopps B, Mericskay M, Gierschik P, Biessen EA, Weber C. SDF-1alpha/CXCR4 axis is instrumental in neointimal hyperplasia and recruitment of smooth muscle progenitor cells. Circ Res. 2005 Apr 15; 96(7): 784-91.
41. Feng Y, Broder CC, Kennedy PE, et al. HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science. 1996; 272(5263): 872-877.
42. Loetscher M, Geiser T, O′Reilly T, et al. Cloning of a human seven transmembrane domain receptor, LESTR, that is highly expressed in leukocytes. J Biol Chem, 1994 ; 269 :232-237.
43. Amara A, Lorthioir O, Valenzuela A, et al. Stromal cell-derived factor-1 associates with heparan sulfates through the first beta-strand of the chemokine. J Biol Chem. 1999; 274: 23916.
44. Nagasawa T, Hirota S, Tachibana K, et al. Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in m ice lacking the CXC chemokine PBSF/SDF-1. Nature. 1996; 382(6592): 635-638.
45. Zou YR, Kottmann AH, Kuroda M, et a1. Function of the chemokine receptor CXCR4 in haematopoiesis and cerebellar developm ent. Nature. 1998; 393(6685):595-599.
46. Ma Q, Jones D, Springer TA. The chemokine receptor CXCR4 is required for the retention of B lineage and granulocytic precursors within the bone marrow microenvironment. Immunity. 1999;10(4):463-471.
47. Juarez J, Bcndall I, Bradstock K, et a1. Chemokines and their receptors as therapeutic targets: the role of the SDF 1/CXCR4 axis. Curr Pharm Des. 2004;10 (11):1245-1259.
48. Majka M, Ratajczak J, Kowalska MA, et a1. Binding of stromal derived factor-lα (SDF-lα) to CXCR4 chemokine receptor in normal human megakaryoblasts but not in platelets induces phosphorylation of mitogen-activated protein kinase p42/44 (MAPK),ELK-1 transcription factor and serine/threonine kinase AKT. Eur J Haematol. 2000; 64(3):164-172.
49. Vila-Coro AJ, Rodriguez-Frade JM, Martin De Ana A, et a1. The chemokine SDF-lα triggers CXCR4 receptor dimerization and activates the JAK/STAT pathway. FASEB J. 1999; 13(13): 1699-1710.
50. Fernandis AZ, Cherla RP, Ganju RK. Differential regulation of CXCR4-mediated T-cell chemotaxis and mitogen-activated protein kinase activation by the membrane tyrosine phosphatase,CD45. J Biol Chem. 2003; 278(11): 9536-9543.
51. Majka M, Janowska-Wieczorek A, Ratajezak J, et a1. Stromal-derived factor 1 and thrombopoietin regulate distinct aspects of hum an megakaryopoiesis. Blood. 2000; 96(13): 4142-4151.
52. Zhang XF, W ang JF, Matczak E, et a1. Janus kinase 2 is involved in stromal cell-derived factor-1 alpha-induced tyrosine phosphorylation of focal adhesion proteins and migration of hematopoietic progenitor cells. Blood. 2001; 97(11): 3342-3348.
53. Kim CH, Hangoc G, Cooper C, et a1. Altered responsiveness to chemokines due to targeted disruption of SHIP. J Clin Invest. 1999; 104(12): 1751-1759.
54. Kim CH,Qu CK, Hangoc G,et a1. Abnormal Chemokine-induced Responses of Immature and Mature Hematopoietic Ce11s from Motheaten Mice Implicate the Protein Tyrosine Phosphatase SHP-1 in Chemokine Responses. J Exp Med. 1999; 190(5): 681—690.
55. Chernock RD, Cherla RP, Ganju RK. SHP2 and cbl participate in a-chemokine receptor CXCR4-mediated signaling pathways. Blood. 2001; 97(3): 608-615.
56. Papayannopoulou T, Current mechanistic scenarios in hematopoietic stem/progenitor cell mobilazation. Blood. 2004; 103: 1580-1585.
57. Vaday GG, Lider O. Extracellular matrix moieties , cytokines , and enzymes: dynamic effects on immune cell behavior and inflammation. J Leukoc Biol. 2000 ; 67 :149-159.
58. Petit I, Kravitz MS, Nagler A, et al. G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and upregulating CXCR4. Nature Immunol. 2002; 3(5):687.
59. Levesque LJ ,Bendall J ,Hendy B ,et al. SDF-1 is inactivated by proteolytic cleavage in the bone marrow of mice mobilized by either G-CSF or cyclophosphamide. Blood. 2001; 98(4): 831.
60. Delgado M, Lewis IC, Loetscher P, et al. Rapid inactivation of stromal cell-derived factor-1 by cathepsin G associated with lymphocytes. Eur J Immunol. 2001; 31 (6): 699.
61. Levesque JP, Hendy J, Takamatsu Y, et al. Disruption of the CXCR4/CXCL12 chemotactic interaction during hematopoietic stem cell mobilization induced by G-CSF or cyclophosphamide. J Clin Invest. 2003; 111:187 – 196.
62. Voermans C , Kooi ML , Rodenhui S ,et al. In vitro migratory capacity of CD34+cells is related to hematopoietic recovery after autologous stem cell transplantation. Blood. 2001; 97 (3):799.
63. Dabusti M, Lanza F, Campioni D, et al. CXCR-4 expression on bone marrow CD34+cells prior to mobilization can predict mobilization adequacy in patients with hematologic malignancies. Hematol Stem Cell Res. 2003; 12(4):425-434.
64. Hattori K, Heissig B, Tashiro K, et al. Plasma elevation of stromal cell-derived factor-1 induces mobilization of mature and immature hematopoietic progenitor and stem cells. Blood. 2001; 97:3354-3360.
65. Perez LE, Alpdogan O, Shieh JH, et al. Increased plasma levels of stromal-derived factor-1 (SDF-1/CXCL12) enhance human thrombopoiesis and mobilize human colony-forming cells (CFC) in NOD/SCID mice. Exp Hematol. 2004 Mar; 32(3):300-7.
66. Pelus LM, Bian H, Fukuda S, et al. The CXCR4 agonist peptide, CTCE-0021, rapidly mobilizes polymorphonuclear neutrophils and hematopoietic progenitor cells into peripheral blood and synergizes with granulocyte colony-stimulating factor. Exp Hematol. 2005 Mar; 33(3):295-307.
67. Sweeney EA, Lortat-Jacob H, Priestley GV, et al. Sulfated polysaccharides increase plasma levels of SDF-1 in monkeys and mice: involvement in mobilization of stem/progenitor cells. Blood. 2002 Jan 1; 99(1):44-51.
68. Togel F, Isaac J, Hu Z, Weiss K, Westenfelder C. Renal SDF-1 signals mobilization and homing of CXCR4-positive cells to the kidney after ischemic injury. Kidney Int.2005 May;67(5):1772-84.
69. Moore M.A, Hattori K, Heissig B, et al. Mobilization of endothelial and hematopoietic stem and progenitor cells by adenovector-mediated elevation of serum levels of SDF-1, VEGF, and angiopoietin-1, Ann N Y Acad Sci. 2001; 938: 36–45.
70. Hiasa K, Ishibashi M, Ohtani K, et al. Gene transfer of stromal cell-derived factor-1alpha enhances ischemic vasculogenesis and angiogenesis via vascular endothelial growth factor/endothelial nitric oxide synthase-related pathway: next-generation chemokine therapy for therapeutic neovascularization, Circulation.2004; 109: 2454–61.
71. De Falco E, Porcelli D, Torella AR, et al. SDF-1 involvement in endothelial phenotype and ischemia-induced recruitment of bone marrow progenitor cells. Blood. 2004; 104: 3472-82.
72. Mohle R, Bautz F, Shalhin R, et al. The chemokine receptor CXCR4 is expressed on CD34+ hematopoietic progenitor and leukemia cells and mediates transendothelial migration induced by stromal cell-derivedfactor-1.Blood. 1998; 91 (12) :4523 - 4530.
73. Aiuti A, Webb IJ, Bleul C, et al. The chemokine SDF-1 is a chemoattractant for human CD34+ hematopoietic progenitor cells and provides a new mechanism to explain the mobilization of CD34+ progenitors to peripheria blood. J Exp Med. 1997; 185 (1):111 - 120.
74. Yamaguchi J, Kusano KF, Masuo O, et al. Stromal cell-derived factor-1 effects on ex vivo expanded endothelial progenitor cells recruitment for ischemic neovascularization. Circulation. 2003; 107:1322-1328.
75. Naiyer JA, Jo DY, Ahn J, et al. Stromal derived fator-1-induced chemokinesis of cord blood CD34 ( + ) cells (long-term culture-initiating cells) through endothelial cells is mediated by E-selectin. Blood. 1999; 94 (12):4011.
76. Voermans C ,Rood PML ,Hordijk PL ,et al. Adhesion molecules involved in transendothelial migration of human hematopoietic progenitor cells. Stem Cells. 2000; 18 (6):435.
77. Peled A, Kollet O, Ponomaryov T, et al. The chemokine SDF-1 activates the intrgrins L FA-1 ,VLA-4 and VLA-5 on immature human CD34 ( + ) cells: role in transendothelial/ stromal migration and engraftment of NOD/ SCID mice. Blood. 2000;95 (11) : 3289-3296.
78. Campbell JJ, Hedrick J, Zlotnik A, et al.Chemokines and the Arrest of Lymphocytes Rolling Under Flow Conditions, Scince 1998;279:381-384.
79. Peled A, Grabovsky V, Habler L, et al. The chemokine SDF-1 stimulates integrin-mediated arrest of CD34 ( + ) cells on vascular endothelium under shear flow. J Clin Invest. 1999; 104 (9) :1199.
80. Peled A, Petit I, Kollet O, et al. Dependence of human stem cell engraftment and repopulation of NOD/ SCID mice on CXCR4. Science. 1999; 283 (5403):845 - 848.
81. Kim CH, Broxmeyer HJ. In vitro behavior of hematopoietic progenitor cells under the influence of chemoattractants: stromal cell-derived factor-1, steel factor, and the bone marrow enviroment. Blood. 1998; 91(1):100 - 110.
82. Hernandez-Lopez C, Varas A, Sacedon R, et a1. Stromal cell-derived factor-1/CXCR4 signaling is critical for early human T-celldevelopment. Blood. 2002; 99(2):546-554.
83. Lataillade JJ, Clay D, Dupuy C, Rigal S, Jasmin C, Bourin P, et al. Chemokine SDF-1 enhances circulating CD34+ cell proliferation in synergy with cytokines: possible role in progenitor survival. Blood. 2000;95:756-68.
84. Hwang JH, Kim SW, Park SE, Yun HJ, Lee Y, Kim S, Jo DY. Overexpression of stromal cell-derived factor-1 enhances endothelium-supported transmigration, maintenance, and proliferation of hematopoietic progenitor cells. Stem Cells Dev. 2006 Apr;15(2):260-8.
85. Gong X, He X, Qi L, Zuo H, Xie Z. Stromal cell derived factor-1 acutely promotes neural progenitor cell proliferation in vitro by a mechanism involving the ERK1/2 and PI-3K signal pathways. Cell Biol Int. 2006 May;30(5):466-71.
86. Broxmeyer HE, Cooper S, Hangoc G, Kim CH. Stromal cell-derived factor-1/CXCL12 selectively counteracts inhibitory effects of myelosuppressive chemokines on hematopoietic progenitor cell proliferation in vitro. Stem Cells Dev. 2005 Apr;14(2):199-203.
87. Lataillade JJ, Domenech J, Le Bousse-Kerdiles MC. Stromal cell-derived factor-1 (SDF-1)\CXCR4 couple plays multiple roles on haematopoietic progenitors at the border between the old cytokine and new chemokine worlds: survival, cell cycling and trafficking. Eur Cytokine Netw. 2004;15:177-88.
88. Lataillade JJ, Clay D, Bourin P, et al. Stromal cell-derived factor 1 regulates primitive hematopoiesis by suppressing apoptosis and by promoting G(0)/G(1) transition in CD34(+) cells: evidence for an autocrine/paracrine mechanism. Blood. 2002; 99: 1117-29.
89. Tan Y, Shao H, Eton D, Yang Z, Alonso-Diaz L, Zhang H, Schulick A, Livingstone AS, Yu H.Stromal cell-derived factor-1 enhances pro-angiogenic effect of granulocyte-colony stimulating factor. Cardiovasc Res. 2007 Mar 1;73(4):823-32.
90. Askari AT, Unzek S, Popovic ZB, et a1. Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic eardiomyopathy. Lancet. 2003; 362(9385): 697-703.
91. Abbott JD, Huang Y, Liu D, et a1. Stromal cell-derived factor-1 alpha plays a critical role in stem cell recruitment to the heart after myocardial infarction but is not suficientto induce homing in the absence of injury. Circulation. 2004; 110(21): 3300-3305.
92. Ma N, Stamm C, Kaminski A, et a1. Human cord blood cells induce angiogenesis following myocardial infarction in NOD/scid-mice. Cardiovasc Res. 2005; 66(1): 45-54.
93. Wang Y, Haider HKh, Ahmad N, Zhang D, Ashraf M. Evidence for ischemia induced host-derived bone marrow cell mobilization into cardiac allografts. J Mol Cell Cardiol. 2006 Sep; 41(3):478-87.
94. Woo YJ, Grand TJ, Berry MF, Atluri P, Moise MA, Hsu VM, Cohen J, Fisher O, Burdick J, Taylor M, Zentko S, Liao G, Smith M, Kolakowski S, Jayasankar V, Gardner TJ, Sweeney HL. Stromal cell-derived factor and granulocyte-monocyte colony-stimulating factor form a combined neovasculogenic therapy for ischemic cardiomyopathy. J Thorac Cardiovasc Surg. 2005 Aug;130(2):321-9.
95. Tang YL, Qian K, Zhang YC, Shen L, Phillips MI. Mobilizing of haematopoietic stem cells to ischemic myocardium by plasmid mediated stromal-cell-derived factor-1alpha (SDF-1alpha) treatment. Regul Pept. 2005 Feb 15;125(1-3):1-8.
96. Zhang G, Nakamura Y, Wang X, Hu Q, Suggs LJ, Zhang J.Controlled Release of Stromal Cell-Derived Factor-1alpha In situ Increases C-kit+ Cell Homing to the Infarcted Heart. Tissue Eng. 2007 Feb 22; [Epub ahead of print]
97. Miller JT, Bartley JH, Wimborne HJ, Walker AL, Hess DC, Hill WD, Carroll JE. The neuroblast and angioblast chemotaxic factor SDF-1 (CXCL12) expression is briefly up regulated by reactive astrocytes in brain following neonatal hypoxic-ischemic injury. BMC Neurosci. 2005 Oct 31;6:63.
98. Hill WD, Hess DC, Martin-Studdard A, Carothers JJ, Zheng J, Hale D, Maeda M, Fagan SC, Carroll JE, Conway SJ. SDF-1 (CXCL12) is upregulated in the ischemic penumbra following stroke: association with bone marrow cell homing to injury. J Neuropathol Exp Neurol. 2004 Jan;63(1):84-96