甲基莲心碱对人血管平滑肌细胞和内皮细胞生长的影响及机制初探
|
摘要
研究背景
高血压和动脉粥样硬化(AS)是心血管领域的主要疾病也是其他相关疾病如冠心病、脑中风等的重要致病因素,其病变基础是以血管平滑肌细胞(VSMC)增生和血管内皮细胞(VEC)受损为主要特征。血管平滑肌细胞的增殖和迁移在高血压病的发展和AS的进展中起着重要的作用。
AngⅡ作为肾素-血管紧张素系统的重要成分,是VSMC增殖和肥大的主要刺激因子。AngⅡ是许多心血管性疾病的重要促进因素,其中部分原因也是由于其对VSMC和VEC的作用。研究显示有多条细胞信号通路参与了AngⅡ对靶细胞的作用。
血红素氧合酶(HO)是血红素分解代谢的起始酶及限速酶,到目前为止被识别的主要有三种,其中HO-1为诱导型。目前的研究提示HO-1在多种细胞的生长、分化等生理和病理过程中起着重要的作用。
甲基莲心碱(Nef)是由睡莲科植物莲的成熟种子的绿色胚芽即中药莲心中提取出的一种生物碱,已有研究发现该类生物碱具有抗心律失常、抗血小板聚集、抗氧自由基等作用。然而,对其详细的分子生物学及细胞生物学机制的尚不清楚,从一定程度上限制了甲基莲心碱临床的应用。目前没有关于甲基莲心碱对VSMC和VEC增殖的影响以及对AngⅡ诱导的细胞信号通路干预作用的报道。
本实验主要探讨甲基莲心碱对人脐静脉平滑肌细胞(HUVSMC)和人脐静脉内皮细胞(HUVEC)生长的影响以及对其可能的作用机制作进一步的探讨。具体的研究内容：1、甲基莲心碱对HUVSMC和HUVEC增殖的影响；2、甲基莲心碱对AngⅡ诱导的HUVSMC和HUVEC生长的影响；3、分析比较在AngⅡ、甲基莲心碱作用下,细胞内HO-1、ERK1/2蛋白表达的变化。
材料与方法
1、培养HUVSMC和HUVEC两个细胞系,MTT法检测不同浓度的甲基莲心碱和AngⅡ对HUVSMC和HUVEC细胞增殖的作用。无血清处理细胞24小时后,分别用甲基莲心碱、ZnPP IX、PD98059等预处理细胞1小时后再与AngⅡ共同孵育细胞24小时,分别做各项相关检测。
2、流式细胞技术检测各处理因素对HUVSMC和HUVEC细胞周期的作用,流式细胞技术Annexin V FITC法检测甲基莲心碱对HUVSMC细胞凋亡率的影响。
3、RT-PCR检测甲基莲心碱和AngⅡ对HUVSMC p21WAF1/CIP1和CyclinD1基因表达水平的作用。
4、Western Blot法检测实验各组作用于HUVSMC和HUVEC 24h后细胞HO-1、ERK1／2蛋白表达和ERK1／2磷酸化水平变化,设GAPDH为内参。
5、硝酸还原酶法测定HUVEC细胞上清液中NO浓度。
6、统计分析：数据均采用SPSS 13.0软件进行统计学处理,结果以均数±SE表示,组间比较用单因素方差分析,多样本均数之间两两比较采用q检验,P<0.05为差异具有显著性意义。
结果
1、甲基莲心碱抑制AngⅡ诱导的HUVSMC增殖
甲基莲心碱能在体外抑制]HUVSMC增殖,且呈浓度时间依赖性。甲基莲心碱不增加HUVSMC细胞凋亡率。甲基莲心碱可有效抑制AngⅡ诱导的HUVSMC的增殖,减少进入S期的细胞数目,使细胞阻滞在G0／G1期。甲基莲心碱(0.5-5.0μmol/L)通过抑制CyclinDl mRNA的表达、促进p21WAF1/CIP1mRNA的表达,使AngⅡ促进的细胞周期进程受阻而拮抗AngⅡ的促HUVSMC增殖作用。
2、甲基莲心碱上调HUVSMC的HO-1表达和抑制ERK1／2的磷酸化
甲基莲心碱可显著诱导HUVSMC的HO-1蛋白的表达,呈剂量依赖趋势。5μmol/L甲基莲心碱可显著对抗AngⅡ诱导的HO-1表达的减低,同时减弱AngⅡ诱导的ERK1／2磷酸化和细胞增殖。甲基莲心碱的这三种作用均能被HO-1特异性抑制剂ZnPP IX所抑制,此外,ZnPP IX还能进一步促进AngⅡ诱导的ERK1／2磷酸化和细胞增殖。HO-1诱导剂CoPP,则可明显减弱AngⅡ诱导的ERK1／2磷酸化和细胞增殖。ERK阻断剂PD98059可明显减弱AngⅡ对HUVSMC诱导的ERK1／2磷酸化和细胞增殖作用,并阻止ZnPP IX诱导的HUVSMC增殖和显著逆转ZnPP IX诱导ERK1／2磷酸化。
3、甲基莲心碱诱导HUVEC增殖及NO的分泌
不同浓度(0.1、0.5、1.0、5.0μmol/L)的甲基莲心碱在作用12h、24h、48h后均可诱导HUVEC明显的增生。甲基莲心碱与HUVEC增殖指数的增加呈一定的浓度依赖趋势。ZnPP IX可部分逆转甲基莲心碱的促HUVEC增殖的作用。甲基莲心碱上调HUVEC内HO-1的表达和ERK1／2的磷酸化水平,并明显增加NO的分泌。PD98059和ZnPP IX对甲基莲心碱诱导的ERK1／2磷酸化的上调均有明显的逆转作用,而对HO-1的表达无影响。
结论
1、甲基莲心碱可在体外抑制HUVSMC的增殖,并通过抑制CyclinDl mRNA的表达,促进P21WAF1/CIP1mRNA的表达而抑制Angll诱导的HUVSMC增殖。
2、Angll可抑制体外培养的HUVEC的生长,甲基莲心碱可诱导体外培养的HUVEC的增殖并对抗Angll的生长抑制作用。
3、甲基莲心碱可通过上调HO-1的表达抑制]HUVSMC的ERK1／2磷酸化。
4、甲基莲心碱可上调HUVEC的HO-1表达和ERK1／2的磷酸化。
5、甲基莲心碱可对抗Angll诱导的HUVEC的NO分泌减少。
Introduction
Proliferation and migration of vascular smooth muscle cells (VSMCs) and endothelial injury play a pivotal role in the development of hypertension and in the progression of atherosclerosis. A vital stimulus for VSMC proliferation and hypertrophy is angiotensinⅡ(AngⅡ), the main effector of the renin-angiotensin system. AngⅡis an important contributing factor to many vascular diseases, in part through its effects on VSMCs and vascular endothelial cells (VECs).Provious studies indicate that many signal molecular, such as mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinase (ERK)1/2 and P38 have been shown to be implicated in the hypertrophic respense of VSMC to AngⅡ.
Heme oxygenases (HOs) are the rate-limiting enzymes in the degradation of heme into carbon monoxide, iron, and biliverdin. To date, three distinct members of the HO-family have been identified. HO-1 is highly inducible by a variety of compounds and different physiologic and pathophysiologic stimuli. Data from current studies suggest that HO-1 plays a vital role in control of cell growth and differentiation.
Neferine is a bis-benzylisoquinoline alkaloid extracted from the green seed embryo of Nelumbo nucifera Gaertn, which is effective in preventing the onset of reentrant ventricular tachyarrhythmias. Neferine can inhibit very low density lipoprotein oxidation and platelet aggregation, protect VECs from damage induced by oxygen free radicals. Neferine was shown to exert biological effects on the cardiovascular system consistant with a Calcium channel blocker. However, the precise mechanism of anti-artherosclerosis by which this drug affects the growth of VSMCs and VECs remains obscure. No studies exist that address the effect of neferine on VSMC and VEC proliferation or the interference of neferine with Ang II-induced signaling pathway.
Therefore, the aim of this study was to test whether neferine affected the growth of HUVSMCs and HUVECs as well as to identify the underlying signaling pathways in HUVSMCs and HUVECs.To test this assuption, this study was as follows:1) to characterize the effect of neferine on cell proliferation in HUVSMCs and HUVECs; 2) to explore the effect of neferine on cell proliferation induced by AngⅡin HUVSMCs and HUVECs; 3) The role of HO-1 and ERK1/2 signal pathway in the cardioprotective effect of neferine was also investigated.
Material and Methods
1、The two cell lines:HUVSMC and HUVEC were cultured. Cell proliferation were detected by the MTT assay and flow cytometry analysis. HUVSMCs or HUVECs were respectively pretreated with neferine, ZnPPⅨ, PD98059 for 1h followed by a stimulation with AngⅡfor 24h.
2、Cell cycle status of HUVSMC or HUVEC was analyzed with a FACScan flow cytometer by measuring fluorescence from cells stained with propidium iodide.The percentages of cells in the different phases of the cell cycle was analyzed using ModFit 3.0 software. The percentage of apoptosis of HUVSMCs was detected by Annexin V-FITC and PI staining with flow cytometry.
3、The gene expressions of p21 WAF1/CIP1 and CyclinDl were detected by RT-PCR at 24h after neferine and or AngⅡin the treated HUVSMC.
4、The phosphorylated and total ERK1/2 proteins and HO-1 protein expression were analyzed by Western Blot at 24h in the treated HUVSMC and HUVEC. For normalization, blots were reprobed with antibodies to detect total amounts of GAPDH.
5、NO concentrations in the HUVEC supernatants were detected by using NO enzyme-immunoassay kit based on nitrate reductase method.
6、Statistical analysis:Analysed were performed using the SPSS(13.0) statistical software package. Results are expressed as means±SE. Data were analyzed using one-way analysis of variance (ANOVA) followed by the Student Newman-Keuls post hoc Tukey test. Differences between groups were considered to be significant at P<0.05.
Result
1. Neferine inhibited AngⅡ-induced proliferation Of HUVSMC
Compared to the control group, neferine decreased the HUVSMC proliferation in a concentration-dependent manner. Neferine did not increase the percentage of apoptosis of HUVSMC.The proliferation of HUVSMC incubated with AngⅡwas significantly attenuated in the presence of neferine. The antiproliferative effect of neferine was confirmed by cell cycle analysis and the cell percentage of S and G2/M phase decreased. Neferine(0.5-5.0μmol/L) arrested HUVSMCs at the G0/G1 phase through suppressing CyclinDl and promoting p21WAF1/CIP1 mRNA expression.
2. Neferine increased HO-1 protein expression and inhibited p-ERKl/2 in HUVSMC stimulated by AngⅡ
Neferine remarkably induced the expression of HO-1 in a concentration-dependant manner when compared to the control in HUVSMC. Coapplication of neferine(5.0μmol/L) with ZnPP IX significantly inhibited neferine-induced HO-1 expression in cells treated with AngⅡ. The inhibitory effect of neferine on AngⅡ-induced cell proliferation and increased p-ERK1/2 was significantly reversed by ZnPP IX. Moreover, CoPP, a HO-1 inducer, was also capable of preventing AngⅡ-induced proliferation in HUVSMCs, whereas ZnPP IX increased it. Perincubation with PD98059 also decreased of AngⅡ-induced cell proliferation in HUVSMCs. PD98059 inhibited the increase in cell proliferation induced by ZnPP IX.
3. Neferine induced HUVEC proliferation and increased the secretion of NO in HUVEC.
Compared to the control group, neferine(0.1,0.5,1.0,5.0μmol/L) increased HUVEC proliferation on 12h,24h,48h and promoted the cell cycle in a concentration-dependent manner. Neferine caused the up-regulation of HO-1 expression and increased the secretion of NO in HUVEC. ERK1/2 phosphorylation was significantly increased compared with the control in HUVEC. Coapplication of neferine with ZnPP IX significantly inhibited neferine-induced HO-1 expression and proliferation in HUVEC. PD98059 and ZnPP IX did not affect neferine-induced HO-1 expression,but reversed up-regulated ERK1/2 phosphorylation induced by neferine.
Conclusion
1、Neferine is capable of inhibiting HUVSMC proliferation and AngⅡ-induced HUVSMC proliferation in vitro. Neferine inhibits the gene expression of CyclinDl mRNA and promotes p21WAF1/CIP1 mRNA expression in AngⅡ-induced HUVSMC.
2、AngⅡinhibites the growth of HUVEC in vitro. Neferine promotes HUVEC proliferation and against AngⅡ-induced inhibitory proliferation.
3、Neferine up-regulates HO-1 expression and inhibits the phosphorylation of ERK1/2 in HUVSMC.
4、Neferine up-regulates HO-1 expression and the phosphorylation of ERK1/2 in HUVEC.
5、Neferine can attenuate the decreased the secretion of NO induced by AngⅡin HUVEC.
高血压和动脉粥样硬化(AS)是心血管领域的主要疾病也是其他相关疾病如冠心病、脑中风等的重要致病因素,其病变基础是以血管平滑肌细胞(VSMC)增生和血管内皮细胞(VEC)受损为主要特征。血管平滑肌细胞的增殖和迁移在高血压病的发展和AS的进展中起着重要的作用。
AngⅡ作为肾素-血管紧张素系统的重要成分,是VSMC增殖和肥大的主要刺激因子。AngⅡ是许多心血管性疾病的重要促进因素,其中部分原因也是由于其对VSMC和VEC的作用。研究显示有多条细胞信号通路参与了AngⅡ对靶细胞的作用。
血红素氧合酶(HO)是血红素分解代谢的起始酶及限速酶,到目前为止被识别的主要有三种,其中HO-1为诱导型。目前的研究提示HO-1在多种细胞的生长、分化等生理和病理过程中起着重要的作用。
甲基莲心碱(Nef)是由睡莲科植物莲的成熟种子的绿色胚芽即中药莲心中提取出的一种生物碱,已有研究发现该类生物碱具有抗心律失常、抗血小板聚集、抗氧自由基等作用。然而,对其详细的分子生物学及细胞生物学机制的尚不清楚,从一定程度上限制了甲基莲心碱临床的应用。目前没有关于甲基莲心碱对VSMC和VEC增殖的影响以及对AngⅡ诱导的细胞信号通路干预作用的报道。
本实验主要探讨甲基莲心碱对人脐静脉平滑肌细胞(HUVSMC)和人脐静脉内皮细胞(HUVEC)生长的影响以及对其可能的作用机制作进一步的探讨。具体的研究内容：1、甲基莲心碱对HUVSMC和HUVEC增殖的影响；2、甲基莲心碱对AngⅡ诱导的HUVSMC和HUVEC生长的影响；3、分析比较在AngⅡ、甲基莲心碱作用下,细胞内HO-1、ERK1/2蛋白表达的变化。
材料与方法
1、培养HUVSMC和HUVEC两个细胞系,MTT法检测不同浓度的甲基莲心碱和AngⅡ对HUVSMC和HUVEC细胞增殖的作用。无血清处理细胞24小时后,分别用甲基莲心碱、ZnPP IX、PD98059等预处理细胞1小时后再与AngⅡ共同孵育细胞24小时,分别做各项相关检测。
2、流式细胞技术检测各处理因素对HUVSMC和HUVEC细胞周期的作用,流式细胞技术Annexin V FITC法检测甲基莲心碱对HUVSMC细胞凋亡率的影响。
3、RT-PCR检测甲基莲心碱和AngⅡ对HUVSMC p21WAF1/CIP1和CyclinD1基因表达水平的作用。
4、Western Blot法检测实验各组作用于HUVSMC和HUVEC 24h后细胞HO-1、ERK1／2蛋白表达和ERK1／2磷酸化水平变化,设GAPDH为内参。
5、硝酸还原酶法测定HUVEC细胞上清液中NO浓度。
6、统计分析：数据均采用SPSS 13.0软件进行统计学处理,结果以均数±SE表示,组间比较用单因素方差分析,多样本均数之间两两比较采用q检验,P<0.05为差异具有显著性意义。
结果
1、甲基莲心碱抑制AngⅡ诱导的HUVSMC增殖
甲基莲心碱能在体外抑制]HUVSMC增殖,且呈浓度时间依赖性。甲基莲心碱不增加HUVSMC细胞凋亡率。甲基莲心碱可有效抑制AngⅡ诱导的HUVSMC的增殖,减少进入S期的细胞数目,使细胞阻滞在G0／G1期。甲基莲心碱(0.5-5.0μmol/L)通过抑制CyclinDl mRNA的表达、促进p21WAF1/CIP1mRNA的表达,使AngⅡ促进的细胞周期进程受阻而拮抗AngⅡ的促HUVSMC增殖作用。
2、甲基莲心碱上调HUVSMC的HO-1表达和抑制ERK1／2的磷酸化
甲基莲心碱可显著诱导HUVSMC的HO-1蛋白的表达,呈剂量依赖趋势。5μmol/L甲基莲心碱可显著对抗AngⅡ诱导的HO-1表达的减低,同时减弱AngⅡ诱导的ERK1／2磷酸化和细胞增殖。甲基莲心碱的这三种作用均能被HO-1特异性抑制剂ZnPP IX所抑制,此外,ZnPP IX还能进一步促进AngⅡ诱导的ERK1／2磷酸化和细胞增殖。HO-1诱导剂CoPP,则可明显减弱AngⅡ诱导的ERK1／2磷酸化和细胞增殖。ERK阻断剂PD98059可明显减弱AngⅡ对HUVSMC诱导的ERK1／2磷酸化和细胞增殖作用,并阻止ZnPP IX诱导的HUVSMC增殖和显著逆转ZnPP IX诱导ERK1／2磷酸化。
3、甲基莲心碱诱导HUVEC增殖及NO的分泌
不同浓度(0.1、0.5、1.0、5.0μmol/L)的甲基莲心碱在作用12h、24h、48h后均可诱导HUVEC明显的增生。甲基莲心碱与HUVEC增殖指数的增加呈一定的浓度依赖趋势。ZnPP IX可部分逆转甲基莲心碱的促HUVEC增殖的作用。甲基莲心碱上调HUVEC内HO-1的表达和ERK1／2的磷酸化水平,并明显增加NO的分泌。PD98059和ZnPP IX对甲基莲心碱诱导的ERK1／2磷酸化的上调均有明显的逆转作用,而对HO-1的表达无影响。
结论
1、甲基莲心碱可在体外抑制HUVSMC的增殖,并通过抑制CyclinDl mRNA的表达,促进P21WAF1/CIP1mRNA的表达而抑制Angll诱导的HUVSMC增殖。
2、Angll可抑制体外培养的HUVEC的生长,甲基莲心碱可诱导体外培养的HUVEC的增殖并对抗Angll的生长抑制作用。
3、甲基莲心碱可通过上调HO-1的表达抑制]HUVSMC的ERK1／2磷酸化。
4、甲基莲心碱可上调HUVEC的HO-1表达和ERK1／2的磷酸化。
5、甲基莲心碱可对抗Angll诱导的HUVEC的NO分泌减少。
Introduction
Proliferation and migration of vascular smooth muscle cells (VSMCs) and endothelial injury play a pivotal role in the development of hypertension and in the progression of atherosclerosis. A vital stimulus for VSMC proliferation and hypertrophy is angiotensinⅡ(AngⅡ), the main effector of the renin-angiotensin system. AngⅡis an important contributing factor to many vascular diseases, in part through its effects on VSMCs and vascular endothelial cells (VECs).Provious studies indicate that many signal molecular, such as mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinase (ERK)1/2 and P38 have been shown to be implicated in the hypertrophic respense of VSMC to AngⅡ.
Heme oxygenases (HOs) are the rate-limiting enzymes in the degradation of heme into carbon monoxide, iron, and biliverdin. To date, three distinct members of the HO-family have been identified. HO-1 is highly inducible by a variety of compounds and different physiologic and pathophysiologic stimuli. Data from current studies suggest that HO-1 plays a vital role in control of cell growth and differentiation.
Neferine is a bis-benzylisoquinoline alkaloid extracted from the green seed embryo of Nelumbo nucifera Gaertn, which is effective in preventing the onset of reentrant ventricular tachyarrhythmias. Neferine can inhibit very low density lipoprotein oxidation and platelet aggregation, protect VECs from damage induced by oxygen free radicals. Neferine was shown to exert biological effects on the cardiovascular system consistant with a Calcium channel blocker. However, the precise mechanism of anti-artherosclerosis by which this drug affects the growth of VSMCs and VECs remains obscure. No studies exist that address the effect of neferine on VSMC and VEC proliferation or the interference of neferine with Ang II-induced signaling pathway.
Therefore, the aim of this study was to test whether neferine affected the growth of HUVSMCs and HUVECs as well as to identify the underlying signaling pathways in HUVSMCs and HUVECs.To test this assuption, this study was as follows:1) to characterize the effect of neferine on cell proliferation in HUVSMCs and HUVECs; 2) to explore the effect of neferine on cell proliferation induced by AngⅡin HUVSMCs and HUVECs; 3) The role of HO-1 and ERK1/2 signal pathway in the cardioprotective effect of neferine was also investigated.
Material and Methods
1、The two cell lines:HUVSMC and HUVEC were cultured. Cell proliferation were detected by the MTT assay and flow cytometry analysis. HUVSMCs or HUVECs were respectively pretreated with neferine, ZnPPⅨ, PD98059 for 1h followed by a stimulation with AngⅡfor 24h.
2、Cell cycle status of HUVSMC or HUVEC was analyzed with a FACScan flow cytometer by measuring fluorescence from cells stained with propidium iodide.The percentages of cells in the different phases of the cell cycle was analyzed using ModFit 3.0 software. The percentage of apoptosis of HUVSMCs was detected by Annexin V-FITC and PI staining with flow cytometry.
3、The gene expressions of p21 WAF1/CIP1 and CyclinDl were detected by RT-PCR at 24h after neferine and or AngⅡin the treated HUVSMC.
4、The phosphorylated and total ERK1/2 proteins and HO-1 protein expression were analyzed by Western Blot at 24h in the treated HUVSMC and HUVEC. For normalization, blots were reprobed with antibodies to detect total amounts of GAPDH.
5、NO concentrations in the HUVEC supernatants were detected by using NO enzyme-immunoassay kit based on nitrate reductase method.
6、Statistical analysis:Analysed were performed using the SPSS(13.0) statistical software package. Results are expressed as means±SE. Data were analyzed using one-way analysis of variance (ANOVA) followed by the Student Newman-Keuls post hoc Tukey test. Differences between groups were considered to be significant at P<0.05.
Result
1. Neferine inhibited AngⅡ-induced proliferation Of HUVSMC
Compared to the control group, neferine decreased the HUVSMC proliferation in a concentration-dependent manner. Neferine did not increase the percentage of apoptosis of HUVSMC.The proliferation of HUVSMC incubated with AngⅡwas significantly attenuated in the presence of neferine. The antiproliferative effect of neferine was confirmed by cell cycle analysis and the cell percentage of S and G2/M phase decreased. Neferine(0.5-5.0μmol/L) arrested HUVSMCs at the G0/G1 phase through suppressing CyclinDl and promoting p21WAF1/CIP1 mRNA expression.
2. Neferine increased HO-1 protein expression and inhibited p-ERKl/2 in HUVSMC stimulated by AngⅡ
Neferine remarkably induced the expression of HO-1 in a concentration-dependant manner when compared to the control in HUVSMC. Coapplication of neferine(5.0μmol/L) with ZnPP IX significantly inhibited neferine-induced HO-1 expression in cells treated with AngⅡ. The inhibitory effect of neferine on AngⅡ-induced cell proliferation and increased p-ERK1/2 was significantly reversed by ZnPP IX. Moreover, CoPP, a HO-1 inducer, was also capable of preventing AngⅡ-induced proliferation in HUVSMCs, whereas ZnPP IX increased it. Perincubation with PD98059 also decreased of AngⅡ-induced cell proliferation in HUVSMCs. PD98059 inhibited the increase in cell proliferation induced by ZnPP IX.
3. Neferine induced HUVEC proliferation and increased the secretion of NO in HUVEC.
Compared to the control group, neferine(0.1,0.5,1.0,5.0μmol/L) increased HUVEC proliferation on 12h,24h,48h and promoted the cell cycle in a concentration-dependent manner. Neferine caused the up-regulation of HO-1 expression and increased the secretion of NO in HUVEC. ERK1/2 phosphorylation was significantly increased compared with the control in HUVEC. Coapplication of neferine with ZnPP IX significantly inhibited neferine-induced HO-1 expression and proliferation in HUVEC. PD98059 and ZnPP IX did not affect neferine-induced HO-1 expression,but reversed up-regulated ERK1/2 phosphorylation induced by neferine.
Conclusion
1、Neferine is capable of inhibiting HUVSMC proliferation and AngⅡ-induced HUVSMC proliferation in vitro. Neferine inhibits the gene expression of CyclinDl mRNA and promotes p21WAF1/CIP1 mRNA expression in AngⅡ-induced HUVSMC.
2、AngⅡinhibites the growth of HUVEC in vitro. Neferine promotes HUVEC proliferation and against AngⅡ-induced inhibitory proliferation.
3、Neferine up-regulates HO-1 expression and inhibits the phosphorylation of ERK1/2 in HUVSMC.
4、Neferine up-regulates HO-1 expression and the phosphorylation of ERK1/2 in HUVEC.
5、Neferine can attenuate the decreased the secretion of NO induced by AngⅡin HUVEC.
引文
[1]Massaeli H, Hurtado C, Austria JA, Pierce GN. Increase in nuclear calcium in smooth muscle cells exposed to oxidized low density lipoprotein. Free Radic Res 2001;34(1):9-16.
[2]Lanza GM, Yu X, Winter PM, Abendschein DR, Karukstis KK, Scott MJ, et al. Targeted antiproliferative drug delivery to vascular smooth muscle cells with a magnetic resonance imaging nanoparticle contrast agent:implications for rational therapy of restenosis. Circulation 2002;106(22):2842-7.
[3]Sindermann JR, Verin V, Hopewell JW, Rodemann HP, Hendry JH. Biological aspects of radiation and drug-eluting stents for the prevention of restenosis. Cardiovasc Res 2004;63(1):22-30.
[4]Mintz GS, Popma JJ, Hong MK, Pichard AD, Kent KM, Satler LF, et al. Intravascular ultrasound to discern device-specific effects and mechanisms of restenosis. Am J Cardiol 1996;78(3A):18-22.
[5]Suzuki T, Kopia G, Hayashi S, Bailey LR, Llanos G, Wilensky R, et al. Stent-based delivery of sirolimus reduces neointimal formation in a porcine coronary model. Circulation 2001;104(10):1188-93.
[6]Ross R. The pathogenesis of atherosclerosis:a perspective for the 1990s. Nature 1993;362(6423):801-9.
[7]Yang SH, Sharrocks AD, Whitmarsh AJ. Transcriptional regulation by the MAP kinase signaling cascades. Gene 2003;320:3-21.
[8]Nagata N, Niwa Y, Nakaya Y. A novel 31-amino-acid-length endothelin, ET-1(1-31), can act as a biologically active peptide for vascular smooth muscle cells. Biochem Biophys Res Commun 2000;275(2):595-600.
[9]Pollman MJ, Hall JL, Gibbons GH. Determinants of vascular smooth muscle cell apoptosis after balloon angioplasty injury. Influence of redox state and cell phenotype. Circ Res 1999;84(1):113-21.
[10]Morita T, Kourembanas S. Endothelial cell expression of vasoconstrictors and growth factors is regulated by smooth muscle cell-derived carbon monoxide. J Clin Invest 1995;96(6):2676-82.
[11]Geisterfer AA, Peach MJ, Owens GK. Angiotensin Ⅱ induces hypertrophy, not hyperplasia, of cultured rat aortic smooth muscle cells. Circ Res 1988; 62(4): 749-56.
[12]Daemen MJ, Lombardi DM, Bosman FT, Schwartz SM. Angiotensin Ⅱ induces smooth muscle cell proliferation in the normal and injured rat arterial wall. Circ Res 1991; 68(2):450-6.
[13]Briand V, Riva L, Galzin AM. Characterization of the angiotensin Ⅱ AT1 receptor subtype involved in DNA synthesis in cultured vascular smooth muscle cells. Br J Pharmacol 1994; 112(4):1195-201.
[14]Chen J, Qi J, Chen F, Liu JH, Wang T, Yang J, et al. Relaxation mechanisms of neferine on the rabbit corpus cavernosum tissue in vitro. Asian J Androl 2007;9(6):795-800.
[15]Chen J, Liu JH, Wang T, Xiao HJ, Yin CP, Yang J. Effects of plant extract neferine on cyclic adenosine monophosphate and cyclic guanosine monophosphate levels in rabbit corpus cavernosum in vitro. Asian J Androl 2008;10(2):307-12.
[16]贾菊芳,敖明章,胡本容,等.甲基莲心碱对脂质过氧化和活性氧自由基的作用.同济医科大学学报 1994；23(1)：62-64.
[17]吴捷莉,冯友梅,从容,等.甲基莲心碱在体外对抗脂蛋白的氧化.中国动脉硬化杂志 1999；7(1)：40-43.
[18]Chamley JH, Campbell GR, McConnell JD, Groschel-Stewart U. Comparison of vascular smooth muscle cells from adult human, monkey and rabbit in primary culture and in subculture. Cell Tissue Res 1977;177(4):503-22.
[19]Seger R, Krebs EG. The MAPK signaling cascade. FASEB J 1995;9(9):726-35.
[20]Sjolund M, Hedin U, Sejersen T, Heldin CH, Thyberg J. Arterial smooth muscle cells express platelet-derived growth factor (PDGF) A chain mRNA, secrete a PDGF-like mitogen, and bind exogenous PDGF in a phenotype-and growth state-dependent manner. J Cell Biol 1988;106(2):403-13.
[21]Rovner AS, Murphy RA, Owens GK. Expression of smooth muscle and nonmuscle myosin heavy chains in cultured vascular smooth muscle cells. J Biol Chem 1986;261(31):14740-5.
[22]Edelmann HM, Kuhne C, Petritsch C, Ballou LM. Cell cycle regulation of p70 S6 kinase and p42/p44 mitogen-activated protein kinases in Swiss mouse 3T3 fibroblasts. J Biol Chem 1996;271(2):963-71.
[23]Cho HM, Choi SH, Hwang KC, Oh SY, Kim HG, Yoon DH, et al. The Src/PLC/PKC/MEK/ERK signaling pathway is involved in aortic smooth muscle cell proliferation induced by glycated LDL. Mol Cells 2005;19(1):60-6.
[24]Treisman R. Regulation of transcription by MAP kinase cascades. Curr Opin Cell Biol 1996;8(2):205-15.
[25]Porter AC, Vaillancourt RR. Tyrosine kinase receptor-activated signal transduction pathways which lead to oncogenesis. Oncogene 1998; 17(11): 1343-52.
[26]Takahashi A, Taniguchi T, Ishikawa Y, Yokoyama M. Tranilast inhibits vascular smooth muscle cell growth and intimal hyperplasia by induction of p21 (waf1/cip1/sdi1) and p53. Circ Res 1999;84(5):543-50.
[1]Poss KD, Tonegawa S. Heme oxygenase 1 is required for mammalian iron reutilization. Proc Natl Acad Sci U S A 1997;94(20):10919-24.
[2]Tulis DA, Durante W, Peyton KJ, Evans AJ, Schafer AI. Heme oxygenase-1 attenuates vascular remodeling following balloon injury in rat carotid arteries. Atherosclerosis 2001;155(1):113-22.
[3]Duckers HJ, Boehm M, True AL, Yet SF, San H, Park JL, et al. Heme oxygenase-1 protects against vascular constriction and proliferation. Nat Med 2001;7(6):693-8.
[4]Yet SF, Layne MD, Liu X, Chen YH, Ith B, Sibinga NE, et al. Absence of heme oxygenase-1 exacerbates atherosclerotic lesion formation and vascular remodeling. FASEB J 2003; 17(12):1759-61.
[5]Schillinger M, Exner M, Minar E, Mlekusch W, Mullner M, Mannhalter C, et al. Heme oxygenase-1 genotype and restenosis after balloon angioplasty:a novel vascular protective factor. J Am Coll Cardiol 2004;43(6):950-7.
[6]Zhang M, Zhang BH, Chen L, An W. Overexpression of heme oxygenase-1 protects smooth muscle cells against oxidative injury and inhibits cell proliferation. Cell Res 2002;12(2):123-32.
[7]Mazure NM, Brahimi-Horn MC, Pouyssegur J. Protein kinases and the hypoxia-inducible factor-1, two switches in angiogenesis. Curr Pharm Des 2003;9(7):531-41.
[8]Kushida T, Li Volti G, Quan S, Goodman A, Abraham NG. Role of human heme oxygenase-1 in attenuating TNF-alpha-mediated inflammation injury in endothelial cells. J Cell Biochem 2002;87(4):377-85.
[9]Otterbein LE, Kolls JK, Mantell LL, Cook JL, Alam J, Choi AM. Exogenous administration of heme oxygenase-1 by gene transfer provides protection against hyperoxia-induced lung injury. J Clin Invest 1999; 103(7):1047-54.
[10]Deng YM, Wu BJ, Witting PK, Stocker R. Probucol protects against smooth muscle cell proliferation by upregulating heme oxygenase-1. Circulation 2004; 110(13):1855-60.
[11]Ryter SW, Xi S, Hartsfield CL, Choi AM. Mitogen activated protein kinase (MAPK) pathway regulates heme oxygenase-1 gene expression by hypoxia in vascular cells. Antioxid Redox Signal 2002;4(4):587-92.
[12]Kushida T, LiVolti G, Goodman AI, Abraham NG. TNF-alpha-mediated cell death is attenuated by retrovirus delivery of human heme oxygenase-1 gene into human microvessel endothelial cells. Transplant Proc 2002;34(7):2973-8.
[13]Feng Y, Wu J, Cong R, Wang C, Zong Y, Feng Z. The effect of neferine on foam cell formation by anti-low density lipoprotein oxidation. J Tongji Med Univ 1998;18(3):134-6.
[14]Yu J, Hu WS. [Effects of neferine on platelet aggregation in rabbits]. Yao Xue Xue Bao 1997;32(1):1-4.
[15]Morita T, Perrella MA, Lee ME, Kourembanas S. Smooth muscle cell-derived carbon monoxide is a regulator of vascular cGMP. Proc Natl Acad Sci U S A 1995;92(5):1475-9.
[16]Otterbein LE, Bach FH, Alam J, Soares M, Tao Lu H, Wysk M, et al. Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway. Nat Med 2000;6(4):422-8.
[17]Abraham NG, Jiang S, Yang L, Zand BA, Laniado-Schwartzman M, Marji J, et al. Adenoviral vector-mediated transfer of human heme oxygenase in rats decreases renal heme-dependent arachidonic acid epoxygenase activity. J Pharmacol Exp Ther 2000;293(2):494-500.
[18]Song HJ, Shin CY, Oh TY, Sohn UD. The protective effect of eupatilin on indomethacin-induced cell damage in cultured feline ileal smooth muscle cells: involvement of HO-1 and ERK. J Ethnopharmacol 2008;118(1):94-101.
[19]Tsui TY, Wu X, Lau CK, Ho DW, Xu T, Siu YT, et al. Prevention of chronic deterioration of heart allograft by recombinant adeno-associated virus-mediated heme oxygenase-1 gene transfer. Circulation 2003;107(20):2623-9.
[20]Schwer CI, Guerrero AM, Humar M, Roesslein M, Goebel U, Stoll P, et al. Heme oxygenase-1 inhibits the proliferation of pancreatic stellate cells by repression of the extracellular signal-regulated kinase 1/2 pathway. J Pharmacol Exp Ther 2008;327(3):863-71.
[21]Pae HO, Jeong GS, Jeong SO, Kim HS, Kim SA, Kim YC, et al. Roles of heme oxygenase-1 in curcumin-induced growth inhibition in rat smooth muscle cells. Exp Mol Med 2007;39(3):267-77.
[22]Woo SW, Lee SH, Ko G, Kim YC, Sohn DH. Isoliquiritigenin inhibits cell proliferation by a heme oxygenase-dependent pathway in rat hepatic stellate cells. Planta Med 2008;74(8):834-9.
[23]Juan SH, Lee TS, Tseng KW, Liou JY, Shyue SK, Wu KK, et al. Adenovirus-mediated heme oxygenase-1 gene transfer inhibits the development of atherosclerosis in apolipoprotein E-deficient mice. Circulation 2001;104(13):1519-25.
[24]Marinissen MJ, Tanos T, Bolos M, de Sagarra MR, Coso OA, Cuadrado A. Inhibition of heme oxygenase-1 interferes with the transforming activity of the Kaposi sarcoma herpesvirus-encoded G protein-coupled receptor. J Biol Chem 2006;281(16):11332-46.
[25]Taille C, Almolki A, Benhamed M, Zedda C, Megret J, Berger P, et al. Heme oxygenase inhibits human airway smooth muscle proliferation via a bilirubin-dependent modulation of ERK1/2 phosphorylation. J Biol Chem 2003;278(29):27160-8.
[26]Li Volti G, Wang J, Traganos F, Kappas A, Abraham NG. Differential effect of heme oxygenase-1 in endothelial and smooth muscle cell cycle progression. Biochem Biophys Res Commun 2002;296(5):1077-82.
[27]Weber H, Taylor DS, Molloy CJ. Angiotensin Ⅱ induces delayed mitogenesis and cellular proliferation in rat aortic smooth muscle cells. Correlation with the expression of specific endogenous growth factors and reversal by suramin. J Clin Invest 1994;93(2):788-98.
[28]Seshiah PN, Weber DS, Rocic P, Valppu L, Taniyama Y, Griendling KK. Angiotensin II stimulation of NAD(P)H oxidase activity:upstream mediators. Circ Res 2002;91(5):406-13.
[29]Saward L, Zahradka P. Angiotensin Ⅱ activates phosphatidylinositol 3-kinase in vascular smooth muscle cells. Circ Res 1997;81(2):249-57.
[30]Chiou WF, Chen CC, Wei BL.3,4-Di-O-Caffeoylquinic Acid Inhibits Angiotensin-II-induced Vascular Smooth Muscle Cell Proliferation and Migration by Downregulating the JNK and PI3K/Akt Signaling Pathways. Evid Based Complement Alternat Med 2009.
[31]Mulder KM. Role of Ras and Mapks in TGFbeta signaling. Cytokine Growth Factor Rev 2000;11(1-2):23-35.
[32]Besson A, Davy A, Robbins SM, Yong VW. Differential activation of ERKs to focal adhesions by PKC epsilon is required for PMA-induced adhesion and migration of human glioma cells. Oncogene 2001;20(50):7398-407.
[33]Sang N, Stiehl DP, Bohensky J, Leshchinsky I, Srinivas V, Caro J. MAPK signaling up-regulates the activity of hypoxia-inducible factors by its effects on p300. J Biol Chem 2003;278(16):14013-9.
[34]Sacerdoti D, Escalante B, Abraham NG, McGiff JC, Levere RD, Schwartzman ML. Treatment with tin prevents the development of hypertension in spontaneously hypertensive rats. Science 1989;243(4889):388-90.
[35]Da Silva JL, Tiefenthaler M, Park E, Escalante B, Schwartzman ML, Levere RD, et al. Tin-mediated heme oxygenase gene activation and cytochrome P450 arachidonate hydroxylase inhibition in spontaneously hypertensive rats. Am J Med Sci 1994;307(3):173-81.
[36]Andreadi CK, Howells LM, Atherfold PA, Manson MM. Involvement of Nrf2, p38, B-Raf, and nuclear factor-kappaB, but not phosphatidylinositol 3-kinase, in induction of hemeoxygenase-1 by dietary polyphenols. Mol Pharmacol 2006;69(3):1033-40.
[37]Cobb MH, Goldsmith EJ. How MAP kinases are regulated. J Biol Chem 1995;270(25):14843-6.
[38]Lee TS, Chang CC, Zhu Y, Shyy JY. Simvastatin induces heme oxygenase-1:a novel mechanism of vessel protection. Circulation 2004; 110(10):1296-302.
[39]El Mabrouk M, Touyz RM, Schiffrin EL. Differential ANG Ⅱ-induced growth activation pathways in mesenteric artery smooth muscle cells from SHR. Am J Physiol Heart Circ Physiol 2001;281(1):H30-9.
[40]Bokemeyer D, Schmitz U, Kramer HJ. Angiotensin Ⅱ-induced growth of vascular smooth muscle cells requires an Src-dependent activation of the epidermal growth factor receptor. Kidney Int 2000;58(2):549-58.
[41]Eguchi S, Numaguchi K, Iwasaki H, Matsumoto T, Yamakawa T, Utsunomiya H, et al. Calcium-dependent epidermal growth factor receptor transactivation mediates the angiotensin II-induced mitogen-activated protein kinase activation in vascular smooth muscle cells. J Biol Chem 1998;273(15):8890-6.
[42]Liao DF, Monia B, Dean N, Berk BC. Protein kinase C-zeta mediates angiotensin II activation of ERK1/2 in vascular smooth muscle cells. J Biol Chem 1997;272(10):6146-50.
[43]Muscella A, Greco S, Elia MG, Storelli C, Marsigliante S. PKC-zeta is required for angiotensin Ⅱ-induced activation of ERK and synthesis of C-FOS in MCF-7 cells. J Cell Physiol 2003;197(1):61-8.
[44]Zhao Y, Liu J, Li L, Liu L, Wu L. Role of Ras/PKCzeta/MEK/ERK1/2 signaling pathway in angiotensin II-induced vascular smooth muscle cell proliferation. Regul Pept 2005;128(1):43-50.
[45]Kim TJ, Lee JH, Lee JJ, Yu JY, Hwang BY, Ye SK, et al. Corynoxeine isolated from the hook of Uncaria rhynchophylla inhibits rat aortic vascular smooth muscle cell proliferation through the blocking of extracellular signal regulated kinase 1/2 phosphorylation. Biol Pharm Bull 2008;31(11):2073-8.
[46]Chen QW, Edvinsson L, Xu CB. Role of ERK/MAPK in endothelin receptor signaling in human aortic smooth muscle cells. BMC Cell Biol 2009; 10:52.
[47]Notoya M, Nishimura H, Woo JT, Nagai K, Ishihara Y, Hagiwara H. Curcumin inhibits the proliferation and mineralization of cultured osteoblasts. Eur J Pharmacol 2006;534(1-3):55-62.
[48]Touyz RM, Schiffrin EL. Increased generation of superoxide by angiotensin II in smooth muscle cells from resistance arteries of hypertensive patients:role of phospholipase D-dependent NAD(P)H oxidase-sensitive pathways. J Hypertens 2001;19(7):1245-54.
[49]Laufs U, Adam O, Strehlow K, Wassmann S, Konkol C, Laufs K, et al. Down-regulation of Rac-1 GTPase by Estrogen. J Biol Chem 2003;278(8):5956-62.
[50]Kim JE, Kang YJ, Lee KY, Choi HC. Isoproterenol inhibits angiotensin II-stimulated proliferation and reactive oxygen species production in vascular smooth muscle cells through heme oxygenase-1. Biol Pharm Bull 2009;32(6): 1047-52.
[51]Wedgwood S, Black SM. Role of reactive oxygen species in vascular remodeling associated with pulmonary hypertension. Antioxid Redox Signal 2003;5(6):759-69.
[52]Naughton P, Foresti R, Bains SK, Hoque M, Green CJ, Motterlini R. Induction of heme oxygenase 1 by nitrosative stress. A role for nitroxyl anion. J Biol Chem 2002;277(431):40666-74.
[53]Maulik N, Engelman DT, Watanabe M, Engelman RM, Das DK. Nitric oxide--a retrograde messenger for carbon monoxide signaling in ischemic heart. Mol Cell Biochem 1996;157(1-2):75-86.
[54]Mehta PK, Griendling KK. Angiotensin II cell signaling:physiological and pathological effects in the cardiovascular system. Am J Physiol Cell Physiol 2007;292(1):C82-97.
[55]Gryglewski RJ, Palmer RM, Moncada S. Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor. Nature 1986;320(6061):454-6.
[56]Rubanyi GM, Vanhoutte PM. Superoxide anions and hyperoxia inactivate endothelium-derived relaxing factor. Am J Physiol 1986;250(sPt 2):H822-7.
[1]Malik FS, Lavie CJ, Mehra MR, Milani RV, Re RN. Renin-angiotensin system: genes to bedside. Am Heart J 1997; 134(3):514-26.
[2]Rakugi H, Yu H, Kamitani A, Nakamura Y, Ohishi M, Kamide K, et al. Links between hypertension and myocardial infarction. Am Heart J 1996;132(1 Pt 2 Su):213-21.
[3]Cines DB, Pollak ES, Buck CA, Loscalzo J, Zimmerman GA, McEver RP, et al. Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood 1998;91(10):3527-61.
[4]Luscher TF. Vascular protection:current possibilities and future perspectives. Int J Clin Pract Suppl 2001(117):3-6.
[5]Vanhoutte PM. Endothelial dysfunction and atherosclerosis. Eur Heart J 1997; 18 Suppl E:E19-29.
[6]Gibbons GH. The pathophysiology of hypertension:the importance of angiotensin II in cardiovascular remodeling. Am J Hypertens 1998; 11(11 Pt 2):177S-81S.
[7]Russo F, Marci M, Raffa S. [Physiopathology of angiotensin II and vascular lesion]. Clin Ter 1997;148(11):537-41.
[8]Asamizu S, Urakaze M, Kobashi C, Ishiki M, Norel Din AK, Fujisaka S, et al. Angiotensin II enhances the increase in monocyte chemoattractant protein-1 production induced by tumor necrosis factor-{alpha} from 3T3-L1 preadipocytes. J Endocrinol 2009;202(2):199-205.
[9]Dimmeler S, Rippmann V, Weiland U, Haendeler J, Zeiher AM. Angiotensin II induces apoptosis of human endothelial cells. Protective effect of nitric oxide. Circ Res 1997;81(6):970-6.
[10]Qian JQ. Cardiovascular pharmacological effects of bisbenzylisoquinoline alkaloid derivatives. Acta Pharmacol Sin 2002;23(12):1086-92.
[11]李瑞峰,温海涛,李莉,陈融,任冬梅,郭成浩,等.半边莲不同组分对内皮细胞内皮素及内皮源一氧化氮合酶代谢的影响.中国动脉硬化杂志,2002,10(1)：19-22
[12]Wu S, Sun C, Cao X, Zhou H, Hong Z, Pan Y. Preparative counter-current chromatography isolation of liensinine and its analogues from embryo of the seed of Nelumbo nucifera GAERTN. using upright coil planet centrifuge with four multilayer coils connected in series. J Chromatogr A 2004;1041(1-2):153-62.
[13]Chen J, Liu JH, Wang T, Xiao HJ, Yin CP, Yang J. Effects of plant extract neferine on cyclic adenosine monophosphate and cyclic guanosine monophosphate levels in rabbit corpus cavernosum in vitro. Asian J Androl 2008;10(2):307-12.
[14]吴远明,胡本蓉,贾菊芳,等.甲基莲心碱对电解性氧自由基损伤离体大鼠心脏的保护作用.中国药理学通报1996；12(4)：325-328.
[15]Peichev M, Naiyer AJ, Pereira D, Zhu Z, Lane WJ, Williams M, et al. Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. Blood 2000;95(3):952-8.
[16]Russo G, Leopold JA, Loscalzo J. Vasoactive substances:nitric oxide and endothelial dysfunction in atherosclerosis. Vascul Pharmacol 2002;38(5):259-69.
[17]Nakayama M, Takahashi K, Kitamuro T, Yasumoto K, Katayose D, Shirato K, et al. Repression of heme oxygenase-1 by hypoxia in vascular endothelial cells. Biochem Biophys Res Commun 2000;271(13):665-71.
[18]Siow RC, Sato H, Mann GE. Heme oxygenase-carbon monoxide signalling pathway in atherosclerosis:anti-atherogenic actions of bilirubin and carbon monoxide? Cardiovasc Res 1999;41(2):385-94.
[19]Zhang M, Zhang BH, Chen L, An W. Overexpression of heme oxygenase-1 protects smooth muscle cells against oxidative injury and inhibits cell proliferation. Cell Res 2002; 12(2):123-32.
[20]Li Volti G, Wang J, Traganos F, Kappas A, Abraham NG. Differential effect of heme oxygenase-1 in endothelial and smooth muscle cell cycle progression. Biochem Biophys Res Commun 2002;296(5):1077-82.
[21]Choi BM, Kim BR. Upregulation of heme oxygenase-1 by brazilin via the phosphatidylinositol 3-kinase/Akt and ERK pathways and its protective effect against oxidative injury. Eur J Pharmacol 2008;580(1-2):12-8.
[22]Hsieh CH, Jeng SF, Hsieh MW, Chen YC, Rau CS, Lu TH, et al. Statin-induced heme oxygenase-1 increases NF-kappaB activation and oxygen radical production in cultured neuronal cells exposed to lipopolysaccharide. Toxicol Sci 2008; 102(1):150-9.
[23]Marinisssen MJ, Tanos T, Bolos M, de Sagarra MR, Coso OA, Cuadrado A. Inhibition of heme oxygenase-1 interferes with the transforming activity of the Kaposi sarcoma herpesvirus-encoded G protein-coupled receptor. J Biol Chem 2006;281(16):11332-46.
[24]Duckers HJ, Boehm M, True AL, et al. Heme oxygenase-1 protects against vascular constriction and proliferation.Nat Med 2001; 7(6):693-8.
[25]Li VG, Wang J, Traganos F, Kappas A, Abraham NG. Differential effect of heme oxygenase-1 in endothelial and smooth muscle cell cycle progression. Biolchem Biophys Res Commun 2002; 296(5):1077-82.
[26]Taille C, Almolki A, Benhamed M, et al. Heme oxygenase inhibits human airway smooth muscle proliferation via a bilirubin-dependent modulation of ERK1/2 phosphorylation. J Biol Chem 2003;278(29):27160-8.
[27]Van Bele E, Banters C, Asahara T, Isner JM. Endothelial regrowth after arterial injury:from vascular repair to therapeutics. Cardiovasc Res 1998;38(1):54-68.
[28]Haider UG, Sorescu D, Griendling KK, Vollmar AM, Dirsch VM. Resveratrol suppresses angiotensin Ⅱ-induced Akt/protein kinase B and p70 S6 kinase phosphorylation and subsequent hypertrophy in rat aortic smooth muscle cells. Mol Pharmacol 2002;62(4):772-7.
[29]Walther T, Menrad A, Orzechowski HD, Siemeister G, Paul M, Schirner M. Differential regulation of in vivo angiogenesis by angiotensin II receptors. Faseb J 2003;17(14):2061-7.
[30]Monton M, Castilla MA, Alvarez Arroyo MV, Tan D, Gonzalez-Pacheco FR, Lopez Farre A, et al. Effects of angiotensin Ⅱ on endothelial cell growth:role of AT-1 and AT-2 receptors. J Am Soc Nephrol 1998;9(6):969-74.
[31]Stoll M, Steckelings UM, Paul M, Bottari SP, Metzger R, Unger T. The angiotensin AT2-receptor mediates inhibition of cell proliferation in coronary endothelial cells. J Clin Invest 1995;95(2):651-7.
[32]Vasa M, Fichtlscherer S, Aicher A, Adler K, Urbich C, Martin H, et al. Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease. Circ Res 2001;89(1):El-7.
[33]Zheng J, Bird IM, Chen DB, Magness RR. Angiotensin 11 regulation of ovine fetoplacental artery endothelial functions:interactions with nitric oxide. J Physiol 2005;565(Pt 1):59-69.
[34]Davies MG, Fulton GJ, Hagen PO. Clinical biology of nitric oxide. Br J Surg 1995;82(12):1598-610.
[35]Hida A, Kawakami A, Miyashita T, Yamasaki S, Nakashima K, Tanaka F, et al. Nitric oxide acts on the mitochondria and protects human endothelial cells from apoptosis. J Lab Clin Med 2004; 144(3):148-55.
[1]Thyberg J, Hedin U, Sjolund M, Palmberg L, Bottger BA. Regulation of differentiated properties and proliferation of arterial smooth muscle cells. Arteriosclerosis 1990;10(6):966-90.
[2]Arai H, Escobedo JA. Angiotensin Ⅱ type 1 receptor signals through Raf-1 by a protein kinase C-dependent, Ras-independent mechanism. Mol Pharmacol 1996;50(3):522-8.
[3]Cobb MH, Goldsmith EJ. How MAP kinases are regulated. J Biol Chem 1995;270(25):14843-6.
[4]Robinson MJ, Cobb MH. Mitogen-activated protein kinase pathways. Curr Opin Cell Biol 1997;9(2):180-6.
[5]Watts SW. Activation of the mitogen-activated protein kinase pathway via the 5-HT2A receptor. Ann N Y Acad Sci 1998;861:162-8.
[6]Cullen PJ, Lockyer PJ. Integration of calcium and Ras signalling. Nat Rev Mol Cell Biol 2002;3(5):339-48.
[7]Crespo P, Xu N, Simonds WF, Gutkind JS. Ras-dependent activation of MAP kinase pathway mediated by G-protein beta gamma subunits. Nature 1994; 369(6479):418-20.
[8]Lopez-Ilasaca M. Signaling from G-protein-coupled receptors to mitogen-activated protein (MAP)-kinase cascades. Biochem Pharmacol 1998;56(3):269-77.
[9]Dong C, Davis RJ, Flavell RA. Signaling by the JNK group of MAP kinases. c-jun N-terminal Kinase. J Clin Immunol 2001;21(4):253-7.
[10]Pearson G, Robinson F, Beers Gibson T, Xu BE, Karandikar M, Berman K, et al. Mitogen-activated protein (MAP) kinase pathways:regulation and physiological functions. Endocr Rev 2001;22(2):153-83.
[11]Xia Z, Dickens M, Raingeaud J, Davis RJ, Greenberg ME. Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 1995;270(5240):1326-31.
[12]Fettucciari K, Fetriconi I, Bartoli A, Rossi R, Marconi P. Involvement of mitogen-activated protein kinases in Group B Streptococcus-induced macrophage apoptosis. Pharmacol Res 2003;47(4):355-62.
[13]Mondorf UF, Geiger H, Herrero M, Zeuzem S, Piiper A. Involvement of the platelet-derived growth factor receptor in angiotensin Ⅱ-induced activation of extracellular regulated kinases 1 and 2 in human mesangial cells. FEBS Lett 2000;472(1):129-32.
[14]Taniyama Y, Ushio-Fukai M, Hitomi H, Rocic P, Kingsley MJ, Pfahnl C, et al. Role of p38 MAPK and MAPKAPK-2 in angiotensin Ⅱ-induced Akt activation in vascular smooth muscle cells. Am J Physiol Cell Physiol 2004;287(2):C494-9.
[15]Horio T, Kohno M, Kano H, Ikeda M, Yasunari K, Yokokawa K, et al. Adrenomedullin as a novel antimigration factor of vascular smooth muscle cells. Circ Res 1995;77(4):660-4.
[16]Ali S, Becker MW, Davis MG, Dorn GW,2nd. Dissociation of vasoconstrictor-stimulated basic fibroblast growth factor expression from hypertrophic growth in cultured vascular smooth muscle cells. Relevant roles of protein kinase C. Circ Res 1994;75(5):836-43.
[17]Duan C, Bauchat JR, Hsieh T. Phosphatidylinositol 3-kinase is required for insulin-like growth factor-Ⅰ-induced vascular smooth muscle cell proliferation and migration. Circ Res 2000;86(1):15-23.
[18]Marrero MB, Schieffer B, Paxton WG, Heerdt L, Berk BC, Delafontaine P, et al. Direct stimulation of Jak/STAT pathway by the angiotensin Ⅱ AT1 receptor. Nature 1995;375(6528):247-50.
[19]Goncharova EA, Ammit AJ, Irani C, Carroll RG, Eszterhas AJ, Panettieri RA, et al. PI3K is required for proliferation and migration of human pulmonary vascular smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 2002;283(2): L354-63.
[20]Nicholl SM, Roztocil E, Davies MG. Urokinase-induced smooth muscle cell responses require distinct signaling pathways:a role for the epidermal growth factor receptor. J Vasc Surg 2005;41(4):672-81.
[21]Seki Y, Kai H, Shibata R, Nagata T, Yasukawa H, Yoshimura A, et al. Role of the JAK/STAT pathway in rat carotid artery remodeling after vascular injury. Circ Res 2000;87(1):12-8.
[22]Foshay K, Rodriguez G, Hoel B, Narayan J, Gallicano GI. JAK2/STAT3 directs cardiomyogenesis within murine embryonic stem cells in vitro. Stem Cells 2005;23(4):530-43.
[23]Zhang S, Yang Y, Kone BC, Allen JC, Kahn AM. Insulin-stimulated cyclic guanosine monophosphate inhibits vascular smooth muscle cell migration by inhibiting Ca/calmodulin-dependent protein kinase Ⅱ. Circulation 2003; 107(11): 1539-44.
[24]杨永键,张鑫,周兴文,等.3种钙激动剂促培养的大鼠血管平滑肌细胞增殖.中国病理生理杂志2001；17(12)：1160-1162.
[1]Struijker-Boudier HA, Smits JF, De Mey JG. Pharmacology of cardiac and vascular remodeling. Annu Rev Pharmacol Toxicol 1995; 35:509-39.
[2]Gibbons GH, Dzau VJ. The emerging concept of vascular remodeling. N Engl J Med 1994; 330(20):1431-8.
[3]Yoshida Y, Mitsumata M, Yamane T, Tomikawa M, Nishida K. Morphology and increased growth rate of atherosclerotic intimal smooth-muscle cells. Arch Pathol Lab Med 1988; 112(10):987-96.
[4]苏海霞.血管损伤后平滑肌细胞表型转变及其研究进展.国外医学2002；29(1)：10-13.
[5]Raines EW, Ross R. Smooth muscle cells and the pathogenesis of the lesions of atherosclerosis. Br Heart J 1993; 69(1 Suppl):S30-7.
[6]Faries PL, Rohan DI, Wyers MC, et al. Vascular smooth muscle cells derived from atherosclerotic human arteries exhibit greater adhesion, migration, and proliferation than venous cells. J Surg Res 2002; 104(1):22-8.
[7]Weir L, Chen D, Pastore C, Isner JM, Walsh K. Expression of gax, a growth arrest homeobox gene, is rapidly down-regulated in the rat carotid artery during the proliferative response to balloon injury. J Biol Chem 1995; 270(10):5457-61.
[8]Firulli AB, Miano JM, Bi W, et al. Myocyte enhancer binding factor-2 expression and activity in vascular smooth muscle cells. Association with the activated phenotype. Circ Res 1996; 78(2):196-204.
[9]Huang SH, Adamis AP, Wiederschain DG, Shima DT, Shing Y, Moses MA. Matrix metalloproteinases and their inhibitors in aqueous humor. Exp Eye Res 1996; 62(5):481-90.
[10]Ramirez Correa GA, Zacchigna S, Arsic N, et al.. Potent inhibition of arterial intimal hyperplasia by TIMP1 gene transfer using AAV vectors. Mol Ther 2004; 9(6):876-84.
[11]Fuster V, Badimon L, Badimon JJ, Chesebro JH. The pathogenesis of coronary artery disease and the acute coronary syndromes (2). N Engl J Med 1992; 326(5): 310-8.
[12]Califf RM, Fortin DF, Frid DJ, et al. Restenosis after coronary angioplasty:an overview. J Am Coll Cardiol 1991; 17(6 Suppl B):2B-13B.
[13]Rodriguez A, Santaera O, Larribeau M, Sosa MI, Palacios IF. Early decrease in minimal luminal diameter after successful percutaneous transluminal coronary angioplasty predicts late restenosis. Am J Cardiol 1993; 71(16):1391-5.
[14]Geng YJ, Libby P. Evidence for apoptosis in advanced human atheroma. Colocalization with interleukin-1 beta-converting enzyme. Am J Pathol 1995; 147(2):251-66.
[15]Han DK, Haudenschild CC, Hong MK, Tinkle BT, Leon MB, Liau G. Evidence for apoptosis in human atherogenesis and in a rat vascular injury model. Am J Pathol 1995; 147(2):267-77.
[16]Bennett MR, Evan GI, Schwartz SM. Apoptosis of human vascular smooth muscle cells derived from normal vessels and coronary atherosclerotic plaques. J Clin Invest 1995; 95(5):2266-74.
[17]Bjorkerud S, Bjorkerud B, Joelsson M. Structural organization of reconstituted human arterial smooth muscle tissue. Arterioscler Thromb 1994; 14(4):644-51.
[18]Kockx MM, Cambier BA, Bortier HE, et al. Foam cell replication and smooth muscle cell apoptosis in human saphenous vein grafts. Histopathology 1994; 25(4):365-71.
[19]Bjorkerud S, Bjorkerud B. Apoptosis is abundant in human atherosclerotic lesions, especially in inflammatory cells (macrophages and T cells), and may contribute to the accumulation of gruel and plaque instability. Am J Pathol 1996; 149(2):367-80.
[20]Liao Y, Husain A. The chymase-angiotensin system in humans:biochemistry, molecular biology and potential role in cardiovascular diseases. Can J Cardiol 1995; 11 Suppl F:13F-19F.
[2l]王关篙,钱桂生,黄桂君等.外源性CD对大鼠肺动脉平滑肌细胞迁移的影响.中国应用生理学杂志2000；16(2)：169-171.
[22]Griffin SA, Brown WC, MacPherson F, et al. Angiotensin Ⅱ causes vascular hypertrophy in part by a non-pressor mechanism. Hypertension 1991; 17(5): 626-35.
[23]Mitchell KD, Braam B, Navar LG. Hypertensinogenic mechanisms mediated by renal actions of renin-angiotensin system. Hypertension 1992; 19(1 Suppl): 118-27.
[24]Weber H, Taylor DS, Molloy CJ. Angiotensin Ⅱ induces delayed mitogenesis and cellular proliferation in rat aortic smooth muscle cells. Correlation with the expression of specific endogenous growth factors and reversal by suramin. J Clin Invest 1994; 93(2):788-98.
[25]Briand V, Riva L, Galzin AM. Characterization of the angiotensin Ⅱ AT1 receptor subtype involved in DNA synthesis in cultured vascular smooth muscle cells. Br J Pharmacol 1994; 112(4):1195-201.
[26]Hahn AW, Resink TJ, Kern F, Buhler FR. Peptide vasoconstrictors, vessel structure, and vascular smooth-muscle proliferation. J Cardiovasc Pharmacol 1993; 22 Suppl 5:S37-43.
[27]Geisterfer AA, Peach MJ, Owens GK. Angiotensin Ⅱ induces hypertrophy, not hyperplasia, of cultured rat aortic smooth muscle cells. Circ Res 1988; 62(4): 749-56.
[28]Bobik A, Grinpukel S, Little PJ, Grooms A, Jackman G. Angiotensin Ⅱ and noradrenaline increase PDGF-BB receptors and potentiate PDGF-BB stimulated
DNA synthesis in vascular smooth muscle. Biochem Biophys Res Commun 1990; 166(2):580-8.
[29]Daemen MJ, Lombardi DM, Bosman FT, Schwartz SM. Angiotensin Ⅱ induces smooth muscle cell proliferation in the normal and injured rat arterial wall. Circ Res 1991; 68(2):450-6.
[30]Corriu C, Andre P, Schott C, Michel M, Stoclet JC. ANG Ⅱ receptor expression and function during phenotypic modulation of rat aortic smooth muscle cells. Am J Physiol 1994; 266(2 Pt 2):H631-6.
[31]Viswanathan M, Seltzer A, Saavedra JM. Heterogeneous expression of angiotensin Ⅱ AT1 receptors in neointima of rat carotid artery and aorta after balloon catheter injury. Peptides 1994; 15(7):1205-12.
[32]Griendling KK, Alexander RW. The angiotensin (AT1) receptor. Semin Nephrol 1993; 13(6):558-66.
[33]Unger T, Gohlke P. Converting enzyme inhibitors in cardiovascular therapy: current status and future potential. Cardiovasc Res 1994; 28(2):146-58.
[34]Wang BW, Chang H, Shyu KG. Regulation of resistin by cyclic mechanical strech in cultured rat vascular smooth muscle cells. Clin Sci (Lond) 2009; 118(3):221-30.
[35]Li L, Zhou Y, Wang C, Zhao YL, Zhang ZG, Fan D, Cui XB, Wu LL. Src tyrosine kinase regulates angiotensin Ⅱ-induced protein kinase Czeta activation and proliferation in vascular smooth muscle cells. Peptides 2010; 31(6):1159-64.
[36]Zhang GH, Shang QH, Jiang QF, Wu ZB, Liu ZL, Wan WH. Effects of ANP upon ion pump activity and gene expression in aortic smooth muscle cells from spontaneously hypertensive rats. Zhonghua Yi Xue Za Zhi 2009; 89(40):2862-6.
[37]Chen HF, Xie LD, Xu CS. The signal transduction pathways of heat shock protein 27 phosphorylation in vasculat smooth muscle cells. Mol Cell Biochem 2010; 333(1-2):49-56.
[2]Lanza GM, Yu X, Winter PM, Abendschein DR, Karukstis KK, Scott MJ, et al. Targeted antiproliferative drug delivery to vascular smooth muscle cells with a magnetic resonance imaging nanoparticle contrast agent:implications for rational therapy of restenosis. Circulation 2002;106(22):2842-7.
[3]Sindermann JR, Verin V, Hopewell JW, Rodemann HP, Hendry JH. Biological aspects of radiation and drug-eluting stents for the prevention of restenosis. Cardiovasc Res 2004;63(1):22-30.
[4]Mintz GS, Popma JJ, Hong MK, Pichard AD, Kent KM, Satler LF, et al. Intravascular ultrasound to discern device-specific effects and mechanisms of restenosis. Am J Cardiol 1996;78(3A):18-22.
[5]Suzuki T, Kopia G, Hayashi S, Bailey LR, Llanos G, Wilensky R, et al. Stent-based delivery of sirolimus reduces neointimal formation in a porcine coronary model. Circulation 2001;104(10):1188-93.
[6]Ross R. The pathogenesis of atherosclerosis:a perspective for the 1990s. Nature 1993;362(6423):801-9.
[7]Yang SH, Sharrocks AD, Whitmarsh AJ. Transcriptional regulation by the MAP kinase signaling cascades. Gene 2003;320:3-21.
[8]Nagata N, Niwa Y, Nakaya Y. A novel 31-amino-acid-length endothelin, ET-1(1-31), can act as a biologically active peptide for vascular smooth muscle cells. Biochem Biophys Res Commun 2000;275(2):595-600.
[9]Pollman MJ, Hall JL, Gibbons GH. Determinants of vascular smooth muscle cell apoptosis after balloon angioplasty injury. Influence of redox state and cell phenotype. Circ Res 1999;84(1):113-21.
[10]Morita T, Kourembanas S. Endothelial cell expression of vasoconstrictors and growth factors is regulated by smooth muscle cell-derived carbon monoxide. J Clin Invest 1995;96(6):2676-82.
[11]Geisterfer AA, Peach MJ, Owens GK. Angiotensin Ⅱ induces hypertrophy, not hyperplasia, of cultured rat aortic smooth muscle cells. Circ Res 1988; 62(4): 749-56.
[12]Daemen MJ, Lombardi DM, Bosman FT, Schwartz SM. Angiotensin Ⅱ induces smooth muscle cell proliferation in the normal and injured rat arterial wall. Circ Res 1991; 68(2):450-6.
[13]Briand V, Riva L, Galzin AM. Characterization of the angiotensin Ⅱ AT1 receptor subtype involved in DNA synthesis in cultured vascular smooth muscle cells. Br J Pharmacol 1994; 112(4):1195-201.
[14]Chen J, Qi J, Chen F, Liu JH, Wang T, Yang J, et al. Relaxation mechanisms of neferine on the rabbit corpus cavernosum tissue in vitro. Asian J Androl 2007;9(6):795-800.
[15]Chen J, Liu JH, Wang T, Xiao HJ, Yin CP, Yang J. Effects of plant extract neferine on cyclic adenosine monophosphate and cyclic guanosine monophosphate levels in rabbit corpus cavernosum in vitro. Asian J Androl 2008;10(2):307-12.
[16]贾菊芳,敖明章,胡本容,等.甲基莲心碱对脂质过氧化和活性氧自由基的作用.同济医科大学学报 1994；23(1)：62-64.
[17]吴捷莉,冯友梅,从容,等.甲基莲心碱在体外对抗脂蛋白的氧化.中国动脉硬化杂志 1999；7(1)：40-43.
[18]Chamley JH, Campbell GR, McConnell JD, Groschel-Stewart U. Comparison of vascular smooth muscle cells from adult human, monkey and rabbit in primary culture and in subculture. Cell Tissue Res 1977;177(4):503-22.
[19]Seger R, Krebs EG. The MAPK signaling cascade. FASEB J 1995;9(9):726-35.
[20]Sjolund M, Hedin U, Sejersen T, Heldin CH, Thyberg J. Arterial smooth muscle cells express platelet-derived growth factor (PDGF) A chain mRNA, secrete a PDGF-like mitogen, and bind exogenous PDGF in a phenotype-and growth state-dependent manner. J Cell Biol 1988;106(2):403-13.
[21]Rovner AS, Murphy RA, Owens GK. Expression of smooth muscle and nonmuscle myosin heavy chains in cultured vascular smooth muscle cells. J Biol Chem 1986;261(31):14740-5.
[22]Edelmann HM, Kuhne C, Petritsch C, Ballou LM. Cell cycle regulation of p70 S6 kinase and p42/p44 mitogen-activated protein kinases in Swiss mouse 3T3 fibroblasts. J Biol Chem 1996;271(2):963-71.
[23]Cho HM, Choi SH, Hwang KC, Oh SY, Kim HG, Yoon DH, et al. The Src/PLC/PKC/MEK/ERK signaling pathway is involved in aortic smooth muscle cell proliferation induced by glycated LDL. Mol Cells 2005;19(1):60-6.
[24]Treisman R. Regulation of transcription by MAP kinase cascades. Curr Opin Cell Biol 1996;8(2):205-15.
[25]Porter AC, Vaillancourt RR. Tyrosine kinase receptor-activated signal transduction pathways which lead to oncogenesis. Oncogene 1998; 17(11): 1343-52.
[26]Takahashi A, Taniguchi T, Ishikawa Y, Yokoyama M. Tranilast inhibits vascular smooth muscle cell growth and intimal hyperplasia by induction of p21 (waf1/cip1/sdi1) and p53. Circ Res 1999;84(5):543-50.
[1]Poss KD, Tonegawa S. Heme oxygenase 1 is required for mammalian iron reutilization. Proc Natl Acad Sci U S A 1997;94(20):10919-24.
[2]Tulis DA, Durante W, Peyton KJ, Evans AJ, Schafer AI. Heme oxygenase-1 attenuates vascular remodeling following balloon injury in rat carotid arteries. Atherosclerosis 2001;155(1):113-22.
[3]Duckers HJ, Boehm M, True AL, Yet SF, San H, Park JL, et al. Heme oxygenase-1 protects against vascular constriction and proliferation. Nat Med 2001;7(6):693-8.
[4]Yet SF, Layne MD, Liu X, Chen YH, Ith B, Sibinga NE, et al. Absence of heme oxygenase-1 exacerbates atherosclerotic lesion formation and vascular remodeling. FASEB J 2003; 17(12):1759-61.
[5]Schillinger M, Exner M, Minar E, Mlekusch W, Mullner M, Mannhalter C, et al. Heme oxygenase-1 genotype and restenosis after balloon angioplasty:a novel vascular protective factor. J Am Coll Cardiol 2004;43(6):950-7.
[6]Zhang M, Zhang BH, Chen L, An W. Overexpression of heme oxygenase-1 protects smooth muscle cells against oxidative injury and inhibits cell proliferation. Cell Res 2002;12(2):123-32.
[7]Mazure NM, Brahimi-Horn MC, Pouyssegur J. Protein kinases and the hypoxia-inducible factor-1, two switches in angiogenesis. Curr Pharm Des 2003;9(7):531-41.
[8]Kushida T, Li Volti G, Quan S, Goodman A, Abraham NG. Role of human heme oxygenase-1 in attenuating TNF-alpha-mediated inflammation injury in endothelial cells. J Cell Biochem 2002;87(4):377-85.
[9]Otterbein LE, Kolls JK, Mantell LL, Cook JL, Alam J, Choi AM. Exogenous administration of heme oxygenase-1 by gene transfer provides protection against hyperoxia-induced lung injury. J Clin Invest 1999; 103(7):1047-54.
[10]Deng YM, Wu BJ, Witting PK, Stocker R. Probucol protects against smooth muscle cell proliferation by upregulating heme oxygenase-1. Circulation 2004; 110(13):1855-60.
[11]Ryter SW, Xi S, Hartsfield CL, Choi AM. Mitogen activated protein kinase (MAPK) pathway regulates heme oxygenase-1 gene expression by hypoxia in vascular cells. Antioxid Redox Signal 2002;4(4):587-92.
[12]Kushida T, LiVolti G, Goodman AI, Abraham NG. TNF-alpha-mediated cell death is attenuated by retrovirus delivery of human heme oxygenase-1 gene into human microvessel endothelial cells. Transplant Proc 2002;34(7):2973-8.
[13]Feng Y, Wu J, Cong R, Wang C, Zong Y, Feng Z. The effect of neferine on foam cell formation by anti-low density lipoprotein oxidation. J Tongji Med Univ 1998;18(3):134-6.
[14]Yu J, Hu WS. [Effects of neferine on platelet aggregation in rabbits]. Yao Xue Xue Bao 1997;32(1):1-4.
[15]Morita T, Perrella MA, Lee ME, Kourembanas S. Smooth muscle cell-derived carbon monoxide is a regulator of vascular cGMP. Proc Natl Acad Sci U S A 1995;92(5):1475-9.
[16]Otterbein LE, Bach FH, Alam J, Soares M, Tao Lu H, Wysk M, et al. Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway. Nat Med 2000;6(4):422-8.
[17]Abraham NG, Jiang S, Yang L, Zand BA, Laniado-Schwartzman M, Marji J, et al. Adenoviral vector-mediated transfer of human heme oxygenase in rats decreases renal heme-dependent arachidonic acid epoxygenase activity. J Pharmacol Exp Ther 2000;293(2):494-500.
[18]Song HJ, Shin CY, Oh TY, Sohn UD. The protective effect of eupatilin on indomethacin-induced cell damage in cultured feline ileal smooth muscle cells: involvement of HO-1 and ERK. J Ethnopharmacol 2008;118(1):94-101.
[19]Tsui TY, Wu X, Lau CK, Ho DW, Xu T, Siu YT, et al. Prevention of chronic deterioration of heart allograft by recombinant adeno-associated virus-mediated heme oxygenase-1 gene transfer. Circulation 2003;107(20):2623-9.
[20]Schwer CI, Guerrero AM, Humar M, Roesslein M, Goebel U, Stoll P, et al. Heme oxygenase-1 inhibits the proliferation of pancreatic stellate cells by repression of the extracellular signal-regulated kinase 1/2 pathway. J Pharmacol Exp Ther 2008;327(3):863-71.
[21]Pae HO, Jeong GS, Jeong SO, Kim HS, Kim SA, Kim YC, et al. Roles of heme oxygenase-1 in curcumin-induced growth inhibition in rat smooth muscle cells. Exp Mol Med 2007;39(3):267-77.
[22]Woo SW, Lee SH, Ko G, Kim YC, Sohn DH. Isoliquiritigenin inhibits cell proliferation by a heme oxygenase-dependent pathway in rat hepatic stellate cells. Planta Med 2008;74(8):834-9.
[23]Juan SH, Lee TS, Tseng KW, Liou JY, Shyue SK, Wu KK, et al. Adenovirus-mediated heme oxygenase-1 gene transfer inhibits the development of atherosclerosis in apolipoprotein E-deficient mice. Circulation 2001;104(13):1519-25.
[24]Marinissen MJ, Tanos T, Bolos M, de Sagarra MR, Coso OA, Cuadrado A. Inhibition of heme oxygenase-1 interferes with the transforming activity of the Kaposi sarcoma herpesvirus-encoded G protein-coupled receptor. J Biol Chem 2006;281(16):11332-46.
[25]Taille C, Almolki A, Benhamed M, Zedda C, Megret J, Berger P, et al. Heme oxygenase inhibits human airway smooth muscle proliferation via a bilirubin-dependent modulation of ERK1/2 phosphorylation. J Biol Chem 2003;278(29):27160-8.
[26]Li Volti G, Wang J, Traganos F, Kappas A, Abraham NG. Differential effect of heme oxygenase-1 in endothelial and smooth muscle cell cycle progression. Biochem Biophys Res Commun 2002;296(5):1077-82.
[27]Weber H, Taylor DS, Molloy CJ. Angiotensin Ⅱ induces delayed mitogenesis and cellular proliferation in rat aortic smooth muscle cells. Correlation with the expression of specific endogenous growth factors and reversal by suramin. J Clin Invest 1994;93(2):788-98.
[28]Seshiah PN, Weber DS, Rocic P, Valppu L, Taniyama Y, Griendling KK. Angiotensin II stimulation of NAD(P)H oxidase activity:upstream mediators. Circ Res 2002;91(5):406-13.
[29]Saward L, Zahradka P. Angiotensin Ⅱ activates phosphatidylinositol 3-kinase in vascular smooth muscle cells. Circ Res 1997;81(2):249-57.
[30]Chiou WF, Chen CC, Wei BL.3,4-Di-O-Caffeoylquinic Acid Inhibits Angiotensin-II-induced Vascular Smooth Muscle Cell Proliferation and Migration by Downregulating the JNK and PI3K/Akt Signaling Pathways. Evid Based Complement Alternat Med 2009.
[31]Mulder KM. Role of Ras and Mapks in TGFbeta signaling. Cytokine Growth Factor Rev 2000;11(1-2):23-35.
[32]Besson A, Davy A, Robbins SM, Yong VW. Differential activation of ERKs to focal adhesions by PKC epsilon is required for PMA-induced adhesion and migration of human glioma cells. Oncogene 2001;20(50):7398-407.
[33]Sang N, Stiehl DP, Bohensky J, Leshchinsky I, Srinivas V, Caro J. MAPK signaling up-regulates the activity of hypoxia-inducible factors by its effects on p300. J Biol Chem 2003;278(16):14013-9.
[34]Sacerdoti D, Escalante B, Abraham NG, McGiff JC, Levere RD, Schwartzman ML. Treatment with tin prevents the development of hypertension in spontaneously hypertensive rats. Science 1989;243(4889):388-90.
[35]Da Silva JL, Tiefenthaler M, Park E, Escalante B, Schwartzman ML, Levere RD, et al. Tin-mediated heme oxygenase gene activation and cytochrome P450 arachidonate hydroxylase inhibition in spontaneously hypertensive rats. Am J Med Sci 1994;307(3):173-81.
[36]Andreadi CK, Howells LM, Atherfold PA, Manson MM. Involvement of Nrf2, p38, B-Raf, and nuclear factor-kappaB, but not phosphatidylinositol 3-kinase, in induction of hemeoxygenase-1 by dietary polyphenols. Mol Pharmacol 2006;69(3):1033-40.
[37]Cobb MH, Goldsmith EJ. How MAP kinases are regulated. J Biol Chem 1995;270(25):14843-6.
[38]Lee TS, Chang CC, Zhu Y, Shyy JY. Simvastatin induces heme oxygenase-1:a novel mechanism of vessel protection. Circulation 2004; 110(10):1296-302.
[39]El Mabrouk M, Touyz RM, Schiffrin EL. Differential ANG Ⅱ-induced growth activation pathways in mesenteric artery smooth muscle cells from SHR. Am J Physiol Heart Circ Physiol 2001;281(1):H30-9.
[40]Bokemeyer D, Schmitz U, Kramer HJ. Angiotensin Ⅱ-induced growth of vascular smooth muscle cells requires an Src-dependent activation of the epidermal growth factor receptor. Kidney Int 2000;58(2):549-58.
[41]Eguchi S, Numaguchi K, Iwasaki H, Matsumoto T, Yamakawa T, Utsunomiya H, et al. Calcium-dependent epidermal growth factor receptor transactivation mediates the angiotensin II-induced mitogen-activated protein kinase activation in vascular smooth muscle cells. J Biol Chem 1998;273(15):8890-6.
[42]Liao DF, Monia B, Dean N, Berk BC. Protein kinase C-zeta mediates angiotensin II activation of ERK1/2 in vascular smooth muscle cells. J Biol Chem 1997;272(10):6146-50.
[43]Muscella A, Greco S, Elia MG, Storelli C, Marsigliante S. PKC-zeta is required for angiotensin Ⅱ-induced activation of ERK and synthesis of C-FOS in MCF-7 cells. J Cell Physiol 2003;197(1):61-8.
[44]Zhao Y, Liu J, Li L, Liu L, Wu L. Role of Ras/PKCzeta/MEK/ERK1/2 signaling pathway in angiotensin II-induced vascular smooth muscle cell proliferation. Regul Pept 2005;128(1):43-50.
[45]Kim TJ, Lee JH, Lee JJ, Yu JY, Hwang BY, Ye SK, et al. Corynoxeine isolated from the hook of Uncaria rhynchophylla inhibits rat aortic vascular smooth muscle cell proliferation through the blocking of extracellular signal regulated kinase 1/2 phosphorylation. Biol Pharm Bull 2008;31(11):2073-8.
[46]Chen QW, Edvinsson L, Xu CB. Role of ERK/MAPK in endothelin receptor signaling in human aortic smooth muscle cells. BMC Cell Biol 2009; 10:52.
[47]Notoya M, Nishimura H, Woo JT, Nagai K, Ishihara Y, Hagiwara H. Curcumin inhibits the proliferation and mineralization of cultured osteoblasts. Eur J Pharmacol 2006;534(1-3):55-62.
[48]Touyz RM, Schiffrin EL. Increased generation of superoxide by angiotensin II in smooth muscle cells from resistance arteries of hypertensive patients:role of phospholipase D-dependent NAD(P)H oxidase-sensitive pathways. J Hypertens 2001;19(7):1245-54.
[49]Laufs U, Adam O, Strehlow K, Wassmann S, Konkol C, Laufs K, et al. Down-regulation of Rac-1 GTPase by Estrogen. J Biol Chem 2003;278(8):5956-62.
[50]Kim JE, Kang YJ, Lee KY, Choi HC. Isoproterenol inhibits angiotensin II-stimulated proliferation and reactive oxygen species production in vascular smooth muscle cells through heme oxygenase-1. Biol Pharm Bull 2009;32(6): 1047-52.
[51]Wedgwood S, Black SM. Role of reactive oxygen species in vascular remodeling associated with pulmonary hypertension. Antioxid Redox Signal 2003;5(6):759-69.
[52]Naughton P, Foresti R, Bains SK, Hoque M, Green CJ, Motterlini R. Induction of heme oxygenase 1 by nitrosative stress. A role for nitroxyl anion. J Biol Chem 2002;277(431):40666-74.
[53]Maulik N, Engelman DT, Watanabe M, Engelman RM, Das DK. Nitric oxide--a retrograde messenger for carbon monoxide signaling in ischemic heart. Mol Cell Biochem 1996;157(1-2):75-86.
[54]Mehta PK, Griendling KK. Angiotensin II cell signaling:physiological and pathological effects in the cardiovascular system. Am J Physiol Cell Physiol 2007;292(1):C82-97.
[55]Gryglewski RJ, Palmer RM, Moncada S. Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor. Nature 1986;320(6061):454-6.
[56]Rubanyi GM, Vanhoutte PM. Superoxide anions and hyperoxia inactivate endothelium-derived relaxing factor. Am J Physiol 1986;250(sPt 2):H822-7.
[1]Malik FS, Lavie CJ, Mehra MR, Milani RV, Re RN. Renin-angiotensin system: genes to bedside. Am Heart J 1997; 134(3):514-26.
[2]Rakugi H, Yu H, Kamitani A, Nakamura Y, Ohishi M, Kamide K, et al. Links between hypertension and myocardial infarction. Am Heart J 1996;132(1 Pt 2 Su):213-21.
[3]Cines DB, Pollak ES, Buck CA, Loscalzo J, Zimmerman GA, McEver RP, et al. Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood 1998;91(10):3527-61.
[4]Luscher TF. Vascular protection:current possibilities and future perspectives. Int J Clin Pract Suppl 2001(117):3-6.
[5]Vanhoutte PM. Endothelial dysfunction and atherosclerosis. Eur Heart J 1997; 18 Suppl E:E19-29.
[6]Gibbons GH. The pathophysiology of hypertension:the importance of angiotensin II in cardiovascular remodeling. Am J Hypertens 1998; 11(11 Pt 2):177S-81S.
[7]Russo F, Marci M, Raffa S. [Physiopathology of angiotensin II and vascular lesion]. Clin Ter 1997;148(11):537-41.
[8]Asamizu S, Urakaze M, Kobashi C, Ishiki M, Norel Din AK, Fujisaka S, et al. Angiotensin II enhances the increase in monocyte chemoattractant protein-1 production induced by tumor necrosis factor-{alpha} from 3T3-L1 preadipocytes. J Endocrinol 2009;202(2):199-205.
[9]Dimmeler S, Rippmann V, Weiland U, Haendeler J, Zeiher AM. Angiotensin II induces apoptosis of human endothelial cells. Protective effect of nitric oxide. Circ Res 1997;81(6):970-6.
[10]Qian JQ. Cardiovascular pharmacological effects of bisbenzylisoquinoline alkaloid derivatives. Acta Pharmacol Sin 2002;23(12):1086-92.
[11]李瑞峰,温海涛,李莉,陈融,任冬梅,郭成浩,等.半边莲不同组分对内皮细胞内皮素及内皮源一氧化氮合酶代谢的影响.中国动脉硬化杂志,2002,10(1)：19-22
[12]Wu S, Sun C, Cao X, Zhou H, Hong Z, Pan Y. Preparative counter-current chromatography isolation of liensinine and its analogues from embryo of the seed of Nelumbo nucifera GAERTN. using upright coil planet centrifuge with four multilayer coils connected in series. J Chromatogr A 2004;1041(1-2):153-62.
[13]Chen J, Liu JH, Wang T, Xiao HJ, Yin CP, Yang J. Effects of plant extract neferine on cyclic adenosine monophosphate and cyclic guanosine monophosphate levels in rabbit corpus cavernosum in vitro. Asian J Androl 2008;10(2):307-12.
[14]吴远明,胡本蓉,贾菊芳,等.甲基莲心碱对电解性氧自由基损伤离体大鼠心脏的保护作用.中国药理学通报1996；12(4)：325-328.
[15]Peichev M, Naiyer AJ, Pereira D, Zhu Z, Lane WJ, Williams M, et al. Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. Blood 2000;95(3):952-8.
[16]Russo G, Leopold JA, Loscalzo J. Vasoactive substances:nitric oxide and endothelial dysfunction in atherosclerosis. Vascul Pharmacol 2002;38(5):259-69.
[17]Nakayama M, Takahashi K, Kitamuro T, Yasumoto K, Katayose D, Shirato K, et al. Repression of heme oxygenase-1 by hypoxia in vascular endothelial cells. Biochem Biophys Res Commun 2000;271(13):665-71.
[18]Siow RC, Sato H, Mann GE. Heme oxygenase-carbon monoxide signalling pathway in atherosclerosis:anti-atherogenic actions of bilirubin and carbon monoxide? Cardiovasc Res 1999;41(2):385-94.
[19]Zhang M, Zhang BH, Chen L, An W. Overexpression of heme oxygenase-1 protects smooth muscle cells against oxidative injury and inhibits cell proliferation. Cell Res 2002; 12(2):123-32.
[20]Li Volti G, Wang J, Traganos F, Kappas A, Abraham NG. Differential effect of heme oxygenase-1 in endothelial and smooth muscle cell cycle progression. Biochem Biophys Res Commun 2002;296(5):1077-82.
[21]Choi BM, Kim BR. Upregulation of heme oxygenase-1 by brazilin via the phosphatidylinositol 3-kinase/Akt and ERK pathways and its protective effect against oxidative injury. Eur J Pharmacol 2008;580(1-2):12-8.
[22]Hsieh CH, Jeng SF, Hsieh MW, Chen YC, Rau CS, Lu TH, et al. Statin-induced heme oxygenase-1 increases NF-kappaB activation and oxygen radical production in cultured neuronal cells exposed to lipopolysaccharide. Toxicol Sci 2008; 102(1):150-9.
[23]Marinisssen MJ, Tanos T, Bolos M, de Sagarra MR, Coso OA, Cuadrado A. Inhibition of heme oxygenase-1 interferes with the transforming activity of the Kaposi sarcoma herpesvirus-encoded G protein-coupled receptor. J Biol Chem 2006;281(16):11332-46.
[24]Duckers HJ, Boehm M, True AL, et al. Heme oxygenase-1 protects against vascular constriction and proliferation.Nat Med 2001; 7(6):693-8.
[25]Li VG, Wang J, Traganos F, Kappas A, Abraham NG. Differential effect of heme oxygenase-1 in endothelial and smooth muscle cell cycle progression. Biolchem Biophys Res Commun 2002; 296(5):1077-82.
[26]Taille C, Almolki A, Benhamed M, et al. Heme oxygenase inhibits human airway smooth muscle proliferation via a bilirubin-dependent modulation of ERK1/2 phosphorylation. J Biol Chem 2003;278(29):27160-8.
[27]Van Bele E, Banters C, Asahara T, Isner JM. Endothelial regrowth after arterial injury:from vascular repair to therapeutics. Cardiovasc Res 1998;38(1):54-68.
[28]Haider UG, Sorescu D, Griendling KK, Vollmar AM, Dirsch VM. Resveratrol suppresses angiotensin Ⅱ-induced Akt/protein kinase B and p70 S6 kinase phosphorylation and subsequent hypertrophy in rat aortic smooth muscle cells. Mol Pharmacol 2002;62(4):772-7.
[29]Walther T, Menrad A, Orzechowski HD, Siemeister G, Paul M, Schirner M. Differential regulation of in vivo angiogenesis by angiotensin II receptors. Faseb J 2003;17(14):2061-7.
[30]Monton M, Castilla MA, Alvarez Arroyo MV, Tan D, Gonzalez-Pacheco FR, Lopez Farre A, et al. Effects of angiotensin Ⅱ on endothelial cell growth:role of AT-1 and AT-2 receptors. J Am Soc Nephrol 1998;9(6):969-74.
[31]Stoll M, Steckelings UM, Paul M, Bottari SP, Metzger R, Unger T. The angiotensin AT2-receptor mediates inhibition of cell proliferation in coronary endothelial cells. J Clin Invest 1995;95(2):651-7.
[32]Vasa M, Fichtlscherer S, Aicher A, Adler K, Urbich C, Martin H, et al. Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease. Circ Res 2001;89(1):El-7.
[33]Zheng J, Bird IM, Chen DB, Magness RR. Angiotensin 11 regulation of ovine fetoplacental artery endothelial functions:interactions with nitric oxide. J Physiol 2005;565(Pt 1):59-69.
[34]Davies MG, Fulton GJ, Hagen PO. Clinical biology of nitric oxide. Br J Surg 1995;82(12):1598-610.
[35]Hida A, Kawakami A, Miyashita T, Yamasaki S, Nakashima K, Tanaka F, et al. Nitric oxide acts on the mitochondria and protects human endothelial cells from apoptosis. J Lab Clin Med 2004; 144(3):148-55.
[1]Thyberg J, Hedin U, Sjolund M, Palmberg L, Bottger BA. Regulation of differentiated properties and proliferation of arterial smooth muscle cells. Arteriosclerosis 1990;10(6):966-90.
[2]Arai H, Escobedo JA. Angiotensin Ⅱ type 1 receptor signals through Raf-1 by a protein kinase C-dependent, Ras-independent mechanism. Mol Pharmacol 1996;50(3):522-8.
[3]Cobb MH, Goldsmith EJ. How MAP kinases are regulated. J Biol Chem 1995;270(25):14843-6.
[4]Robinson MJ, Cobb MH. Mitogen-activated protein kinase pathways. Curr Opin Cell Biol 1997;9(2):180-6.
[5]Watts SW. Activation of the mitogen-activated protein kinase pathway via the 5-HT2A receptor. Ann N Y Acad Sci 1998;861:162-8.
[6]Cullen PJ, Lockyer PJ. Integration of calcium and Ras signalling. Nat Rev Mol Cell Biol 2002;3(5):339-48.
[7]Crespo P, Xu N, Simonds WF, Gutkind JS. Ras-dependent activation of MAP kinase pathway mediated by G-protein beta gamma subunits. Nature 1994; 369(6479):418-20.
[8]Lopez-Ilasaca M. Signaling from G-protein-coupled receptors to mitogen-activated protein (MAP)-kinase cascades. Biochem Pharmacol 1998;56(3):269-77.
[9]Dong C, Davis RJ, Flavell RA. Signaling by the JNK group of MAP kinases. c-jun N-terminal Kinase. J Clin Immunol 2001;21(4):253-7.
[10]Pearson G, Robinson F, Beers Gibson T, Xu BE, Karandikar M, Berman K, et al. Mitogen-activated protein (MAP) kinase pathways:regulation and physiological functions. Endocr Rev 2001;22(2):153-83.
[11]Xia Z, Dickens M, Raingeaud J, Davis RJ, Greenberg ME. Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 1995;270(5240):1326-31.
[12]Fettucciari K, Fetriconi I, Bartoli A, Rossi R, Marconi P. Involvement of mitogen-activated protein kinases in Group B Streptococcus-induced macrophage apoptosis. Pharmacol Res 2003;47(4):355-62.
[13]Mondorf UF, Geiger H, Herrero M, Zeuzem S, Piiper A. Involvement of the platelet-derived growth factor receptor in angiotensin Ⅱ-induced activation of extracellular regulated kinases 1 and 2 in human mesangial cells. FEBS Lett 2000;472(1):129-32.
[14]Taniyama Y, Ushio-Fukai M, Hitomi H, Rocic P, Kingsley MJ, Pfahnl C, et al. Role of p38 MAPK and MAPKAPK-2 in angiotensin Ⅱ-induced Akt activation in vascular smooth muscle cells. Am J Physiol Cell Physiol 2004;287(2):C494-9.
[15]Horio T, Kohno M, Kano H, Ikeda M, Yasunari K, Yokokawa K, et al. Adrenomedullin as a novel antimigration factor of vascular smooth muscle cells. Circ Res 1995;77(4):660-4.
[16]Ali S, Becker MW, Davis MG, Dorn GW,2nd. Dissociation of vasoconstrictor-stimulated basic fibroblast growth factor expression from hypertrophic growth in cultured vascular smooth muscle cells. Relevant roles of protein kinase C. Circ Res 1994;75(5):836-43.
[17]Duan C, Bauchat JR, Hsieh T. Phosphatidylinositol 3-kinase is required for insulin-like growth factor-Ⅰ-induced vascular smooth muscle cell proliferation and migration. Circ Res 2000;86(1):15-23.
[18]Marrero MB, Schieffer B, Paxton WG, Heerdt L, Berk BC, Delafontaine P, et al. Direct stimulation of Jak/STAT pathway by the angiotensin Ⅱ AT1 receptor. Nature 1995;375(6528):247-50.
[19]Goncharova EA, Ammit AJ, Irani C, Carroll RG, Eszterhas AJ, Panettieri RA, et al. PI3K is required for proliferation and migration of human pulmonary vascular smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 2002;283(2): L354-63.
[20]Nicholl SM, Roztocil E, Davies MG. Urokinase-induced smooth muscle cell responses require distinct signaling pathways:a role for the epidermal growth factor receptor. J Vasc Surg 2005;41(4):672-81.
[21]Seki Y, Kai H, Shibata R, Nagata T, Yasukawa H, Yoshimura A, et al. Role of the JAK/STAT pathway in rat carotid artery remodeling after vascular injury. Circ Res 2000;87(1):12-8.
[22]Foshay K, Rodriguez G, Hoel B, Narayan J, Gallicano GI. JAK2/STAT3 directs cardiomyogenesis within murine embryonic stem cells in vitro. Stem Cells 2005;23(4):530-43.
[23]Zhang S, Yang Y, Kone BC, Allen JC, Kahn AM. Insulin-stimulated cyclic guanosine monophosphate inhibits vascular smooth muscle cell migration by inhibiting Ca/calmodulin-dependent protein kinase Ⅱ. Circulation 2003; 107(11): 1539-44.
[24]杨永键,张鑫,周兴文,等.3种钙激动剂促培养的大鼠血管平滑肌细胞增殖.中国病理生理杂志2001；17(12)：1160-1162.
[1]Struijker-Boudier HA, Smits JF, De Mey JG. Pharmacology of cardiac and vascular remodeling. Annu Rev Pharmacol Toxicol 1995; 35:509-39.
[2]Gibbons GH, Dzau VJ. The emerging concept of vascular remodeling. N Engl J Med 1994; 330(20):1431-8.
[3]Yoshida Y, Mitsumata M, Yamane T, Tomikawa M, Nishida K. Morphology and increased growth rate of atherosclerotic intimal smooth-muscle cells. Arch Pathol Lab Med 1988; 112(10):987-96.
[4]苏海霞.血管损伤后平滑肌细胞表型转变及其研究进展.国外医学2002；29(1)：10-13.
[5]Raines EW, Ross R. Smooth muscle cells and the pathogenesis of the lesions of atherosclerosis. Br Heart J 1993; 69(1 Suppl):S30-7.
[6]Faries PL, Rohan DI, Wyers MC, et al. Vascular smooth muscle cells derived from atherosclerotic human arteries exhibit greater adhesion, migration, and proliferation than venous cells. J Surg Res 2002; 104(1):22-8.
[7]Weir L, Chen D, Pastore C, Isner JM, Walsh K. Expression of gax, a growth arrest homeobox gene, is rapidly down-regulated in the rat carotid artery during the proliferative response to balloon injury. J Biol Chem 1995; 270(10):5457-61.
[8]Firulli AB, Miano JM, Bi W, et al. Myocyte enhancer binding factor-2 expression and activity in vascular smooth muscle cells. Association with the activated phenotype. Circ Res 1996; 78(2):196-204.
[9]Huang SH, Adamis AP, Wiederschain DG, Shima DT, Shing Y, Moses MA. Matrix metalloproteinases and their inhibitors in aqueous humor. Exp Eye Res 1996; 62(5):481-90.
[10]Ramirez Correa GA, Zacchigna S, Arsic N, et al.. Potent inhibition of arterial intimal hyperplasia by TIMP1 gene transfer using AAV vectors. Mol Ther 2004; 9(6):876-84.
[11]Fuster V, Badimon L, Badimon JJ, Chesebro JH. The pathogenesis of coronary artery disease and the acute coronary syndromes (2). N Engl J Med 1992; 326(5): 310-8.
[12]Califf RM, Fortin DF, Frid DJ, et al. Restenosis after coronary angioplasty:an overview. J Am Coll Cardiol 1991; 17(6 Suppl B):2B-13B.
[13]Rodriguez A, Santaera O, Larribeau M, Sosa MI, Palacios IF. Early decrease in minimal luminal diameter after successful percutaneous transluminal coronary angioplasty predicts late restenosis. Am J Cardiol 1993; 71(16):1391-5.
[14]Geng YJ, Libby P. Evidence for apoptosis in advanced human atheroma. Colocalization with interleukin-1 beta-converting enzyme. Am J Pathol 1995; 147(2):251-66.
[15]Han DK, Haudenschild CC, Hong MK, Tinkle BT, Leon MB, Liau G. Evidence for apoptosis in human atherogenesis and in a rat vascular injury model. Am J Pathol 1995; 147(2):267-77.
[16]Bennett MR, Evan GI, Schwartz SM. Apoptosis of human vascular smooth muscle cells derived from normal vessels and coronary atherosclerotic plaques. J Clin Invest 1995; 95(5):2266-74.
[17]Bjorkerud S, Bjorkerud B, Joelsson M. Structural organization of reconstituted human arterial smooth muscle tissue. Arterioscler Thromb 1994; 14(4):644-51.
[18]Kockx MM, Cambier BA, Bortier HE, et al. Foam cell replication and smooth muscle cell apoptosis in human saphenous vein grafts. Histopathology 1994; 25(4):365-71.
[19]Bjorkerud S, Bjorkerud B. Apoptosis is abundant in human atherosclerotic lesions, especially in inflammatory cells (macrophages and T cells), and may contribute to the accumulation of gruel and plaque instability. Am J Pathol 1996; 149(2):367-80.
[20]Liao Y, Husain A. The chymase-angiotensin system in humans:biochemistry, molecular biology and potential role in cardiovascular diseases. Can J Cardiol 1995; 11 Suppl F:13F-19F.
[2l]王关篙,钱桂生,黄桂君等.外源性CD对大鼠肺动脉平滑肌细胞迁移的影响.中国应用生理学杂志2000；16(2)：169-171.
[22]Griffin SA, Brown WC, MacPherson F, et al. Angiotensin Ⅱ causes vascular hypertrophy in part by a non-pressor mechanism. Hypertension 1991; 17(5): 626-35.
[23]Mitchell KD, Braam B, Navar LG. Hypertensinogenic mechanisms mediated by renal actions of renin-angiotensin system. Hypertension 1992; 19(1 Suppl): 118-27.
[24]Weber H, Taylor DS, Molloy CJ. Angiotensin Ⅱ induces delayed mitogenesis and cellular proliferation in rat aortic smooth muscle cells. Correlation with the expression of specific endogenous growth factors and reversal by suramin. J Clin Invest 1994; 93(2):788-98.
[25]Briand V, Riva L, Galzin AM. Characterization of the angiotensin Ⅱ AT1 receptor subtype involved in DNA synthesis in cultured vascular smooth muscle cells. Br J Pharmacol 1994; 112(4):1195-201.
[26]Hahn AW, Resink TJ, Kern F, Buhler FR. Peptide vasoconstrictors, vessel structure, and vascular smooth-muscle proliferation. J Cardiovasc Pharmacol 1993; 22 Suppl 5:S37-43.
[27]Geisterfer AA, Peach MJ, Owens GK. Angiotensin Ⅱ induces hypertrophy, not hyperplasia, of cultured rat aortic smooth muscle cells. Circ Res 1988; 62(4): 749-56.
[28]Bobik A, Grinpukel S, Little PJ, Grooms A, Jackman G. Angiotensin Ⅱ and noradrenaline increase PDGF-BB receptors and potentiate PDGF-BB stimulated
DNA synthesis in vascular smooth muscle. Biochem Biophys Res Commun 1990; 166(2):580-8.
[29]Daemen MJ, Lombardi DM, Bosman FT, Schwartz SM. Angiotensin Ⅱ induces smooth muscle cell proliferation in the normal and injured rat arterial wall. Circ Res 1991; 68(2):450-6.
[30]Corriu C, Andre P, Schott C, Michel M, Stoclet JC. ANG Ⅱ receptor expression and function during phenotypic modulation of rat aortic smooth muscle cells. Am J Physiol 1994; 266(2 Pt 2):H631-6.
[31]Viswanathan M, Seltzer A, Saavedra JM. Heterogeneous expression of angiotensin Ⅱ AT1 receptors in neointima of rat carotid artery and aorta after balloon catheter injury. Peptides 1994; 15(7):1205-12.
[32]Griendling KK, Alexander RW. The angiotensin (AT1) receptor. Semin Nephrol 1993; 13(6):558-66.
[33]Unger T, Gohlke P. Converting enzyme inhibitors in cardiovascular therapy: current status and future potential. Cardiovasc Res 1994; 28(2):146-58.
[34]Wang BW, Chang H, Shyu KG. Regulation of resistin by cyclic mechanical strech in cultured rat vascular smooth muscle cells. Clin Sci (Lond) 2009; 118(3):221-30.
[35]Li L, Zhou Y, Wang C, Zhao YL, Zhang ZG, Fan D, Cui XB, Wu LL. Src tyrosine kinase regulates angiotensin Ⅱ-induced protein kinase Czeta activation and proliferation in vascular smooth muscle cells. Peptides 2010; 31(6):1159-64.
[36]Zhang GH, Shang QH, Jiang QF, Wu ZB, Liu ZL, Wan WH. Effects of ANP upon ion pump activity and gene expression in aortic smooth muscle cells from spontaneously hypertensive rats. Zhonghua Yi Xue Za Zhi 2009; 89(40):2862-6.
[37]Chen HF, Xie LD, Xu CS. The signal transduction pathways of heat shock protein 27 phosphorylation in vasculat smooth muscle cells. Mol Cell Biochem 2010; 333(1-2):49-56.