急性心脑血管血栓性疾病与组织因子途径改变的关系研究
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摘要
许多研究表明,凝血过程在动脉血栓性疾病中起重要作用。关于血液凝固,目前盛行的是两阶段学说,强调体内凝血过程是由组织因子途径(tissue fator pathway, TFP)启动的,然而凝血因子尤其是TFP在心脑血管血栓性疾病中的作用尚未完全阐明。大量实验与临床资料表明组织因子途径抑制物(tissue factor pathway inhibitor, TFPI)和组织因子(tissue factor, TF)失去正常平衡状态,这与血栓性疾病的发生发展密切相关。TF是一种跨膜蛋白质,可与凝血因子Ⅶ(coagulation factorⅦ, FⅦ)结合,并激活FⅦ使之成为活化的FⅦ(activated FⅦ, FⅦa),形成TF-FⅦa复合物,其通过水解激活FⅩ、FⅨ,从而启动凝血过程,导致凝血酶原活化与纤维蛋白的形成。由此可知,TF-FⅦa与TFPI的力量对比决定凝血过程的启动。
近年来,国内外一些研究表明,TFP的改变与心脑血管血栓性疾病密切相关。心脑血管血栓性疾病是目前临床工作中面对的最常见的一组疾病,按病因是动脉粥样硬化及血栓形成,但根本因素是动脉内血栓的形成。TF作为TFP的启动因子,在动脉粥样硬化、冠状动脉疾病的发生中扮演了重要的角色,而TFPI是目前唯一能抑制TF活性的生理性活性物质,在预防血栓形成中起重要作用。TFPI从结构上分为全长(full-length,fl-TFPI)、截短(truncated,tr-TFPI)两型,依其是否已与脂蛋白结合,分为结合型TFPI与游离型TFPI,结合型TFPI抗凝能力很弱,而游离型TFPI则有较强的抗凝能力;依其合成情况而言,TFPI分为TFPIα和TFPIβ。FⅦ从其活性分为酶原与酶两型,TFP各凝血因子不同形式之间比值的变化与心脑血管血栓性疾病的关系尚未见报道。因此,研究TFP与心脑血管疾病及其它血栓性疾病关系成为一个新的方向。另外,外周血中单核细胞(monocytes,Mo)活性增强以及Mo募集到血管内膜,在很大程度上也影响动脉粥样硬化的形成。静息状态下Mo和内皮细胞不表达TF。在病理状态下,内毒素(lypopolysaccharide,LPS)、白介素-1(interleukin-1,IL-1)、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)等炎症因子可诱导Mo表达TF。有报道血管紧张素Ⅱ诱发TF表达及其在人类Mo内的发生机制与核因子-κB(nuclear factor kappa B,NF-κB)激活有关。然而目前尚未见心脑血管疾病中外周血Mo TFmRNA变化的相关报道。中国是一个多民族国家,而新疆是少数民族自治区,在新疆关于急性心脑血管血栓性疾病患者的TFP变化,尚无人问津。
目的:基于上述,本研究的主要内容包括:1)首先对TFPI的二种试剂盒进行比较,选择一种为临床诊断血栓性疾病提供简单、实用的TFPI试剂盒;2)初步观察乌鲁木齐地区健康中老年人汉族、维吾尔族血浆中TFP各成分的水平变化;3)了解急性心肌梗死(acute myocardial infarction,AMI)患者和急性缺血性脑卒中(acute ischemic stroks,AIS)患者发作期间TFP和其它凝血因子的变化及其意义,并观察它们是否存在差异;4)观察AMI及AIS患者发作期间外周血Mo TFmRNA的表达。
方法:1)采用Assaypro和American Diagnostica Inc(ADI)两种TFPI试剂盒检测TFPI抗原水平,并进行定量比较;2)血浆复钙时间采用手工法;3)血浆中TF活性测定采用发色底物法;4)血浆中的TF、TFPI、凝血因子Ⅶ抗原(FⅦAg),激活的FⅦ(FⅦa)及D-二聚体(D-dimer)采用酶联免疫吸附法(enzyme-linked immunosorbent assay ,ELISA);5)凝血因子Ⅶ促凝活性(FⅦ∶C)测定采用一期凝固法;6)采用逆转录聚合酶链式反应(reverse transcription-polymerase chain reaction ,RT-PCR)方法检测Mo TFmRNA水平。
结果:1)两种TFPI检测试剂盒比较:①总TFPI在正常对照组,Assaypro TFPI试剂盒测定为61.65±19.32μg/L , ADI TFPI (﹟ 850 )试剂盒测得结果为87.25±24.5μg/L,可信区间ADI较Assaypro试剂盒接近公认范围;②在AMI组,Assaapro试剂盒测得总TFPI为77.32±32.5μg/L,其可信区间上限未超过正常值参考范围上限,而ADI试剂盒测得总TFPI为115.79±52μg/L,可信区间上限显著超过正常参考范围值上限;③Assaypro试剂盒仅能测得总TFPI,而ADI的TFPI(﹟850)试剂盒可同时测得总TFPI(total,t-TFPI)和fl-TFPI,二者之差又能求出tr-TFPI。因此,ADI试剂盒可测得TFPI三种形式;④在对照组和AMI组两种试剂盒测得t-TFPI的变异系数无统计学差异。
2)乌鲁木齐地区汉族、维吾尔族健康人TFP的初步观察:①汉族人群、维吾尔族人群其TF抗原、t-TFPI、fl-TFPI、TF/t-TFPI、tr-TFPI/fl-TFPI、TF/tr-TFPI比值,FⅦAg、FⅦa、FⅦ∶C和三者之间比值及血浆D-dimer无显著性差异;②与汉族比较,维吾尔族人血浆中tr-TFPI含量、TF/fl-TFPI及tr-TFPI/t-TFPI比值明显降低。
3)AMI和AIS患者发作期间TFP和其它凝血因子的改变及差异:①血浆复钙时间AMI患者和AIS患者均比正常对照者明显缩短;②与对照组比较,AMI患者及AIS患者血浆中TF活性、TF抗原及TFPI抗原均显著增加,但TF增高程度较TFPI更为显著,故TF/TFPI比值升高;与AMI组对比,AIS组中血浆TF活性增高的程度更为显著。关于TFPI,表现为t-TFPI和fl-TFPI含量明显增加,而tr-TFPI含量明显降低;由于TF和TFPI的变化,则TF/t-TFPI、TF/tr-TFPI以及fl-TFPI/t-TFPI比值高于对照组,而TF/fl-TFPI与tr-TFPI/t-TFPI以及tr-TFPI/fl-TFPI比值低于对照组。尽管TFP中大多数因子变化趋势在AMI和AIS组中是一致的,但TF活性在AIS组中明显高于AMI组。③与对照组相比,血浆FⅦ∶C、FⅦa在AMI组是增高的,FⅦAg无显著性变化,FⅦa/FⅦAg比值明显升高,但FⅦa/FⅦ∶C及FⅦ∶C/FⅦAg比值无显著性差异,而在AIS组与对照组相比,FⅦ∶C增高,FⅦa、FⅦAg以及FⅦa/FⅦAg差异无显著性,但FⅦ∶C/FⅦAg比值明显升高,FⅦa/FⅦ∶C比值明显降低;与AMI组相比,FⅦa和FⅦa/FⅦ∶C在AIS组呈下降;④与对照组相比,AMI和AIS组D-dimer均明显增高。
4)AMI及AIS患者发作期间外周血Mo TFmRNA表达:①AMI、AIS组与对照组相比,外周血Mo TFmRNA表达均显著增高;②Mo TFmRNA表达与血浆TF抗原水平明显正相关。
结论:1)ADI的TFPI试剂盒效度明显优于Assaypro TFPI试剂盒;
2)与汉族健康中老年人相比,维吾尔族人血浆TFP成份并无明显差别,但tr-TFPI较低;
3)AMI和AIS患者发作期间体内TFP的启动与血栓事件的发生有密切的相关性;
4)与对照组相比,外周血FⅦ∶C水平在AMI组与AIS组中都显著性升高,而FⅦa和FⅦa/FⅦAg比值仅在AMI组升高。除TF活性外,TFP其余因子的变化趋势在病例组(AMI和AIS)是一致的。提示运用比值(如TF/tr-TFPI ,tr-TFPI/fl-TFPI)的测定可能更敏感,更可靠的评估凝血过程的发生;
5).D-dimer水平是可以反映AMI及AIS患者继发性纤溶活性的一个指标;
6)外周血Mo TFmRNA在急性心脑血管血栓性疾病中呈高表达。
Many studies showed that the blood coagulation process plays an important role in the evolution of acute arterial thrombotic events. A two-stage theory of coagulation is widely accepted.Tissue factor pathway (TFP) is responsible for the initiation of coagulation. However, the contribution of coagulation factors especially in TFP to the development of ischemic arterial disease is still not clearly established. Recent experiments and clinical observations demonstrated that the disturbance of normal balance of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) is closely associated with the evolution of thrombotic episodes. TF is a transmembrane glycoprotein.TF binds factorⅦ(FⅦ) and leads to the activation of factorⅦ(FⅦa) and the formation of TF-FⅦa complex. In turn, TF-FⅦa complex activates factorsⅩandⅨvia limited proteolysis. Therefore, it initiates a cascade of enzymatic reactions resulting ultimately in fibrin clot formation. Therefore, it becomes apparent that the balance of TF-FⅦa and TFPI is a determinant of the initiation of coagulation.
Several recent studies suggested that the changes of TFP are closely associated with thrombosis during the onset of acute cerebrocardiac diseases.The cerebrocardiac thrombotic diseases are one of the most common and serious clinical problem. Two mechanisms are responsible for it: atherosclerosis and thrombosis,but the arterial thrombotic is the principal cause of acute myocardial infarction(AMI) and acute ischemic stroke(AIS). TF initiates the TFP and plays an important role in the pathogenesis of atherosclerosis and coronary artery disease. TFPI is the unique physiological inhibitor of the TF-induced initation of blood coagulation and a key factor to prevent thrombosis.On the basis of the integrity of the structure,TFPI has two types: full-length TFPI (fl-TFPI) and truncated TFPI(tr-TFPI).The latter is truncated at the c-terminal end. According to whether bound to lipoproteins or not,TFPI is divided into two forms:free-TFPI and bound-TFPI. Compared with bound-TFPI, free-TFPI possesses much more anticoagulant activity. TFPI is mainly produced by endothelial cells and alternative mRNA splicing generates two forms: TFPIαand TFPIβ.
Based on catalytic activity, FactorⅦcontains two styles: Zymogen and enzyme. However, up to now, the relationship between the changes of ratios among the different styles(types,forms) of each coagulation parameter and the evaluation of cerebrocardiac thrombotic diseases has been still not reported. Therefore, it is a novel research direction to investigate the association of TFP with the pathogenesis of cerebrocardiac thrombotic diseases and other thrombotic disease. On the other hand, high reactivity of peripheral blood monocyte as well as monocyte recruitment to the intima can strongly affect the development of atherosclerosis.In rest state, monocytes and endothelial cells do not express tissue factor;but under pathological conditions, lypopolysaccharide(LPS),interleukin-1(IL-1),tumor necrosis factor-α(TNF-α) and other proinflammatory agents can induce them to express tissue factor.
It has been reported that angiotensinⅡ(AngⅡ) induced monocytes to express TF and its mechanism was involved NF-κB activation. However, no paper has reported the changes of TFmRNA in monocytes isolated from peripheral blood in patients with cardiovascular and cerebrovascular diseases. The Chinese nation consists of many nationalities and Xinjiang is regional autonomy of minority nationalities.Up to now, the changes of TFP during the onset of acute cerebrocardiac thrombotic diseases have not yet been observed in XinJiang.
Purpose:
The aim of the present study is 1) to select one kind of kits used to detect TFPI, which can offer more efficient and convenient clinical informations about thrombotic diseases; 2) to compare the levels of plasma TFP components in the healthy volunteers of Han nationality and Uygur nationality in Urumqi; 3) to observe the involvement of TFP and other blood coagulation factors during the onset of AIS and AMI, and furthermore, to demonstrate whether there are some differences in the changes of coagulation- anticoagulation system between AMI and AIS; 4) to observe the expression of TF mRNA in monocytes during the onset of AMI and AIS in patients.
Methods:
1) to compare the concentration of TFPI, Assaypro and American Diagnostica Inc (ADI) kits were used to determine the antigen levels.
2) Plasma recalcification time was detected by manual operation.
3)Plasma TF activity was assayed with the chromogenic method.
4) Plasma TF?TFPI and FⅦantigen (FⅦAg) and activated FⅦ(FⅦa) and D-dimer were measured with enzyme linked immunosorbent assay (ELISA).
5) FⅦcoagulation activity (FⅦ∶C) was observed in the one-stage clotting assay.
6) Reverse transcriptase-polymerase chain reaction(RT-PCR) was used to determine the levels of TFmRNA in monocytes.
Results:
1) Comparison of two kinds of TFPI assay kits.
①Total-TFPI (t-TFPI) in plasma isolated from the control group was measured by Assaypro and ADI kits(﹟850) separatively. The data were presented as mean±S.D.i.e. Assayprro: 61.65±19.32μg/L; ADI:87.25±24.5μg/L. The confidence interval tested by ADI kit was more close to the widely accepted reference range of TFPI than that obtained from Assaypro kit in the normal control group.
②The level of total-TFPI measured in patients with AMI by using Assaypro kit was 77.32±32.5μg/L and the upper limit of the confidence interval was below that of the reference range of normal people. However, the level of total-TFPI measured by ADI kit(﹟850) was 115.79±52μg/L, the upper limit of the confidence interval was significantly above that of the reference range of normal people.
③In contrast to assaypro TFPI kit only used to detect total-TFPI,total(t)-TFPI as well as full length(fl)-TFPI were simultaneously measured by using ADI TFPI kit(﹟850) and the difference between t-TFPI and fl-TFPI is truncated(tr)-TFPI.Thus,three parameters about TFPI can be obtained by using ADI TFPI kit(﹟850).
④The differences of the coefficient of variation of total-TFPI measurements obtained from AMI and the normal control groups by two kinds kits were not statistically significant.
2) A preliminary observation of the plasma tissue factor pathway in the healthy volunteers of Han and Urygur nationalities,in Urumqi.
①There were no significant differences in the antigen levels of TF,t-TFPI,fl-TFPI and in the ratios of TF/t-TFPI,TF/tr-TFPI,tr-TFPI/fl-TFPI between the healthy population of Han and Uygur nationalities. The levels of plasma FⅦAg,FⅦa and FⅦ∶C,D-dimer and the ratios among them were not significantly different.
②The concentration of plasma tr-TFPI and the ratios of TF/fl-TFPI and tr-TFPI/t-TFPI in the Uygur nationality group were markedly lower than those in the Han nationality group.
3) Observation on TFP and other coagulation factors during the onset of acute cerebrocardiac thrombotic diseases.
①Plasma recalcification time in AMI and AIS groups was significantly shorter than that in the control group.
②The levels of TF activity and the concentration of TF and TFPI antigen in plasma were significantly higher in the AMI and AIS groups than those in the control group. But the increament degree of TF was remarkably higher than that of TFPI. Therefore, the TF/TFPI ratio was markedly increasead in the AMI and AIS groups.In contrast to the AMI group,the increament degree of TF activity in plasma was markedly higher in the AIS group.As to TFPI, t-TFPI and fl-TFPI were significantly higher; on the contrary, tr-TFPI was markedly lower than that in the control group.Due to the changes of TF and TFPI, the TF/t-TFPI?TF/tr-TFPI and fl-TFPI/t-TFPI ratios were increased and the TF/fl-TFPI, tr-TFPI/t-TFPI and tr-TFPI/fl-TFPI ratios decreased simultaneously in the AMI and AIS groups compared with the control group.Although the tendency of the changes in most parameters of TFP was consistant in the AMI group and the AIS group,the TF activity in the AIS group was remarkably higher than that in the AMI group.
③Compared with the control group,the levels of plasma FⅦ∶C were remarkably increased in AMI and AIS groups. There was no significant difference in FⅦantigen between the AMI and control groups. The concentration of FⅦa and the ratio of FⅦa/FⅦAg were more remarkably higher in the AMI group, whereas the ratio differences of FⅦa/FⅦ∶C or FⅦ∶C/FⅦAg between the control and AMI groups was not significant. On the other hand, there were no significant differences between AIS and control groups in FⅦa, FⅦAg and FⅦa/FⅦAg ratio. But the FⅦ∶C/FⅦAg ratio was remarkably higher and FⅦa/FⅦ∶C ratio was significantly lower than those in the AIS group.In contrast to the AMI group, FⅦa and the ratio of FⅦa/FⅦ∶C were decreased in the AIS group.
④The levels of plasma D-dimer were remarkably increased in the AMI and AIS groups compared with the control group.
4) Observation on the expression and variation of peripheral monocytes TF-mRNA in patients with AMI and AIS:
①The expression of TF mRNA in human peripheral monocytes was significantly higher in the AMI and AIS groups compared with the control group.
②The levels of TF mRNA expression were positively related to the concentration of plasma TF in the three groups.
Conclusions:
1) The ADI kit used for assay of TFPI concentrations can offer more informations about its types than the Assaypro kit.
2) Compared with the age-matched healthy subjects of Han nationality,there was no significant difference in the ingredients of plasma TFP,but the level of tr-TFPI was remarkably lower in the Uygur nationality.
3) During the onset of AMI and AIS, the initiation of TFP is associated with the thrombotic events.
4) In contrast to the control group,the levels of plasma FⅦ∶C were increased in the AMI and AIS groups;but plasma FⅦa and the ratio of FⅦa/FⅦAg were only elevated in the AMI group.Except TF activity, the tendency of the changes of TFP is consistent in both (AMI and AIS)groups.It may be more sensitive and reliable to use the ratios(such as TF/tr-TFPI,tr-TFPI/fl-TFPI)to evaluate the initiation status of coagulation.
5) The level of D-dimer is considered to be a parameter for the secondary activation of fibrinolysis in patients with AIS and AMI.
6) The expression of TFmRNA in monocytes was upregulated during the onset of AMI and AIS.
近年来,国内外一些研究表明,TFP的改变与心脑血管血栓性疾病密切相关。心脑血管血栓性疾病是目前临床工作中面对的最常见的一组疾病,按病因是动脉粥样硬化及血栓形成,但根本因素是动脉内血栓的形成。TF作为TFP的启动因子,在动脉粥样硬化、冠状动脉疾病的发生中扮演了重要的角色,而TFPI是目前唯一能抑制TF活性的生理性活性物质,在预防血栓形成中起重要作用。TFPI从结构上分为全长(full-length,fl-TFPI)、截短(truncated,tr-TFPI)两型,依其是否已与脂蛋白结合,分为结合型TFPI与游离型TFPI,结合型TFPI抗凝能力很弱,而游离型TFPI则有较强的抗凝能力;依其合成情况而言,TFPI分为TFPIα和TFPIβ。FⅦ从其活性分为酶原与酶两型,TFP各凝血因子不同形式之间比值的变化与心脑血管血栓性疾病的关系尚未见报道。因此,研究TFP与心脑血管疾病及其它血栓性疾病关系成为一个新的方向。另外,外周血中单核细胞(monocytes,Mo)活性增强以及Mo募集到血管内膜,在很大程度上也影响动脉粥样硬化的形成。静息状态下Mo和内皮细胞不表达TF。在病理状态下,内毒素(lypopolysaccharide,LPS)、白介素-1(interleukin-1,IL-1)、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)等炎症因子可诱导Mo表达TF。有报道血管紧张素Ⅱ诱发TF表达及其在人类Mo内的发生机制与核因子-κB(nuclear factor kappa B,NF-κB)激活有关。然而目前尚未见心脑血管疾病中外周血Mo TFmRNA变化的相关报道。中国是一个多民族国家,而新疆是少数民族自治区,在新疆关于急性心脑血管血栓性疾病患者的TFP变化,尚无人问津。
目的:基于上述,本研究的主要内容包括:1)首先对TFPI的二种试剂盒进行比较,选择一种为临床诊断血栓性疾病提供简单、实用的TFPI试剂盒;2)初步观察乌鲁木齐地区健康中老年人汉族、维吾尔族血浆中TFP各成分的水平变化;3)了解急性心肌梗死(acute myocardial infarction,AMI)患者和急性缺血性脑卒中(acute ischemic stroks,AIS)患者发作期间TFP和其它凝血因子的变化及其意义,并观察它们是否存在差异;4)观察AMI及AIS患者发作期间外周血Mo TFmRNA的表达。
方法:1)采用Assaypro和American Diagnostica Inc(ADI)两种TFPI试剂盒检测TFPI抗原水平,并进行定量比较;2)血浆复钙时间采用手工法;3)血浆中TF活性测定采用发色底物法;4)血浆中的TF、TFPI、凝血因子Ⅶ抗原(FⅦAg),激活的FⅦ(FⅦa)及D-二聚体(D-dimer)采用酶联免疫吸附法(enzyme-linked immunosorbent assay ,ELISA);5)凝血因子Ⅶ促凝活性(FⅦ∶C)测定采用一期凝固法;6)采用逆转录聚合酶链式反应(reverse transcription-polymerase chain reaction ,RT-PCR)方法检测Mo TFmRNA水平。
结果:1)两种TFPI检测试剂盒比较:①总TFPI在正常对照组,Assaypro TFPI试剂盒测定为61.65±19.32μg/L , ADI TFPI (﹟ 850 )试剂盒测得结果为87.25±24.5μg/L,可信区间ADI较Assaypro试剂盒接近公认范围;②在AMI组,Assaapro试剂盒测得总TFPI为77.32±32.5μg/L,其可信区间上限未超过正常值参考范围上限,而ADI试剂盒测得总TFPI为115.79±52μg/L,可信区间上限显著超过正常参考范围值上限;③Assaypro试剂盒仅能测得总TFPI,而ADI的TFPI(﹟850)试剂盒可同时测得总TFPI(total,t-TFPI)和fl-TFPI,二者之差又能求出tr-TFPI。因此,ADI试剂盒可测得TFPI三种形式;④在对照组和AMI组两种试剂盒测得t-TFPI的变异系数无统计学差异。
2)乌鲁木齐地区汉族、维吾尔族健康人TFP的初步观察:①汉族人群、维吾尔族人群其TF抗原、t-TFPI、fl-TFPI、TF/t-TFPI、tr-TFPI/fl-TFPI、TF/tr-TFPI比值,FⅦAg、FⅦa、FⅦ∶C和三者之间比值及血浆D-dimer无显著性差异;②与汉族比较,维吾尔族人血浆中tr-TFPI含量、TF/fl-TFPI及tr-TFPI/t-TFPI比值明显降低。
3)AMI和AIS患者发作期间TFP和其它凝血因子的改变及差异:①血浆复钙时间AMI患者和AIS患者均比正常对照者明显缩短;②与对照组比较,AMI患者及AIS患者血浆中TF活性、TF抗原及TFPI抗原均显著增加,但TF增高程度较TFPI更为显著,故TF/TFPI比值升高;与AMI组对比,AIS组中血浆TF活性增高的程度更为显著。关于TFPI,表现为t-TFPI和fl-TFPI含量明显增加,而tr-TFPI含量明显降低;由于TF和TFPI的变化,则TF/t-TFPI、TF/tr-TFPI以及fl-TFPI/t-TFPI比值高于对照组,而TF/fl-TFPI与tr-TFPI/t-TFPI以及tr-TFPI/fl-TFPI比值低于对照组。尽管TFP中大多数因子变化趋势在AMI和AIS组中是一致的,但TF活性在AIS组中明显高于AMI组。③与对照组相比,血浆FⅦ∶C、FⅦa在AMI组是增高的,FⅦAg无显著性变化,FⅦa/FⅦAg比值明显升高,但FⅦa/FⅦ∶C及FⅦ∶C/FⅦAg比值无显著性差异,而在AIS组与对照组相比,FⅦ∶C增高,FⅦa、FⅦAg以及FⅦa/FⅦAg差异无显著性,但FⅦ∶C/FⅦAg比值明显升高,FⅦa/FⅦ∶C比值明显降低;与AMI组相比,FⅦa和FⅦa/FⅦ∶C在AIS组呈下降;④与对照组相比,AMI和AIS组D-dimer均明显增高。
4)AMI及AIS患者发作期间外周血Mo TFmRNA表达:①AMI、AIS组与对照组相比,外周血Mo TFmRNA表达均显著增高;②Mo TFmRNA表达与血浆TF抗原水平明显正相关。
结论:1)ADI的TFPI试剂盒效度明显优于Assaypro TFPI试剂盒;
2)与汉族健康中老年人相比,维吾尔族人血浆TFP成份并无明显差别,但tr-TFPI较低;
3)AMI和AIS患者发作期间体内TFP的启动与血栓事件的发生有密切的相关性;
4)与对照组相比,外周血FⅦ∶C水平在AMI组与AIS组中都显著性升高,而FⅦa和FⅦa/FⅦAg比值仅在AMI组升高。除TF活性外,TFP其余因子的变化趋势在病例组(AMI和AIS)是一致的。提示运用比值(如TF/tr-TFPI ,tr-TFPI/fl-TFPI)的测定可能更敏感,更可靠的评估凝血过程的发生;
5).D-dimer水平是可以反映AMI及AIS患者继发性纤溶活性的一个指标;
6)外周血Mo TFmRNA在急性心脑血管血栓性疾病中呈高表达。
Many studies showed that the blood coagulation process plays an important role in the evolution of acute arterial thrombotic events. A two-stage theory of coagulation is widely accepted.Tissue factor pathway (TFP) is responsible for the initiation of coagulation. However, the contribution of coagulation factors especially in TFP to the development of ischemic arterial disease is still not clearly established. Recent experiments and clinical observations demonstrated that the disturbance of normal balance of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) is closely associated with the evolution of thrombotic episodes. TF is a transmembrane glycoprotein.TF binds factorⅦ(FⅦ) and leads to the activation of factorⅦ(FⅦa) and the formation of TF-FⅦa complex. In turn, TF-FⅦa complex activates factorsⅩandⅨvia limited proteolysis. Therefore, it initiates a cascade of enzymatic reactions resulting ultimately in fibrin clot formation. Therefore, it becomes apparent that the balance of TF-FⅦa and TFPI is a determinant of the initiation of coagulation.
Several recent studies suggested that the changes of TFP are closely associated with thrombosis during the onset of acute cerebrocardiac diseases.The cerebrocardiac thrombotic diseases are one of the most common and serious clinical problem. Two mechanisms are responsible for it: atherosclerosis and thrombosis,but the arterial thrombotic is the principal cause of acute myocardial infarction(AMI) and acute ischemic stroke(AIS). TF initiates the TFP and plays an important role in the pathogenesis of atherosclerosis and coronary artery disease. TFPI is the unique physiological inhibitor of the TF-induced initation of blood coagulation and a key factor to prevent thrombosis.On the basis of the integrity of the structure,TFPI has two types: full-length TFPI (fl-TFPI) and truncated TFPI(tr-TFPI).The latter is truncated at the c-terminal end. According to whether bound to lipoproteins or not,TFPI is divided into two forms:free-TFPI and bound-TFPI. Compared with bound-TFPI, free-TFPI possesses much more anticoagulant activity. TFPI is mainly produced by endothelial cells and alternative mRNA splicing generates two forms: TFPIαand TFPIβ.
Based on catalytic activity, FactorⅦcontains two styles: Zymogen and enzyme. However, up to now, the relationship between the changes of ratios among the different styles(types,forms) of each coagulation parameter and the evaluation of cerebrocardiac thrombotic diseases has been still not reported. Therefore, it is a novel research direction to investigate the association of TFP with the pathogenesis of cerebrocardiac thrombotic diseases and other thrombotic disease. On the other hand, high reactivity of peripheral blood monocyte as well as monocyte recruitment to the intima can strongly affect the development of atherosclerosis.In rest state, monocytes and endothelial cells do not express tissue factor;but under pathological conditions, lypopolysaccharide(LPS),interleukin-1(IL-1),tumor necrosis factor-α(TNF-α) and other proinflammatory agents can induce them to express tissue factor.
It has been reported that angiotensinⅡ(AngⅡ) induced monocytes to express TF and its mechanism was involved NF-κB activation. However, no paper has reported the changes of TFmRNA in monocytes isolated from peripheral blood in patients with cardiovascular and cerebrovascular diseases. The Chinese nation consists of many nationalities and Xinjiang is regional autonomy of minority nationalities.Up to now, the changes of TFP during the onset of acute cerebrocardiac thrombotic diseases have not yet been observed in XinJiang.
Purpose:
The aim of the present study is 1) to select one kind of kits used to detect TFPI, which can offer more efficient and convenient clinical informations about thrombotic diseases; 2) to compare the levels of plasma TFP components in the healthy volunteers of Han nationality and Uygur nationality in Urumqi; 3) to observe the involvement of TFP and other blood coagulation factors during the onset of AIS and AMI, and furthermore, to demonstrate whether there are some differences in the changes of coagulation- anticoagulation system between AMI and AIS; 4) to observe the expression of TF mRNA in monocytes during the onset of AMI and AIS in patients.
Methods:
1) to compare the concentration of TFPI, Assaypro and American Diagnostica Inc (ADI) kits were used to determine the antigen levels.
2) Plasma recalcification time was detected by manual operation.
3)Plasma TF activity was assayed with the chromogenic method.
4) Plasma TF?TFPI and FⅦantigen (FⅦAg) and activated FⅦ(FⅦa) and D-dimer were measured with enzyme linked immunosorbent assay (ELISA).
5) FⅦcoagulation activity (FⅦ∶C) was observed in the one-stage clotting assay.
6) Reverse transcriptase-polymerase chain reaction(RT-PCR) was used to determine the levels of TFmRNA in monocytes.
Results:
1) Comparison of two kinds of TFPI assay kits.
①Total-TFPI (t-TFPI) in plasma isolated from the control group was measured by Assaypro and ADI kits(﹟850) separatively. The data were presented as mean±S.D.i.e. Assayprro: 61.65±19.32μg/L; ADI:87.25±24.5μg/L. The confidence interval tested by ADI kit was more close to the widely accepted reference range of TFPI than that obtained from Assaypro kit in the normal control group.
②The level of total-TFPI measured in patients with AMI by using Assaypro kit was 77.32±32.5μg/L and the upper limit of the confidence interval was below that of the reference range of normal people. However, the level of total-TFPI measured by ADI kit(﹟850) was 115.79±52μg/L, the upper limit of the confidence interval was significantly above that of the reference range of normal people.
③In contrast to assaypro TFPI kit only used to detect total-TFPI,total(t)-TFPI as well as full length(fl)-TFPI were simultaneously measured by using ADI TFPI kit(﹟850) and the difference between t-TFPI and fl-TFPI is truncated(tr)-TFPI.Thus,three parameters about TFPI can be obtained by using ADI TFPI kit(﹟850).
④The differences of the coefficient of variation of total-TFPI measurements obtained from AMI and the normal control groups by two kinds kits were not statistically significant.
2) A preliminary observation of the plasma tissue factor pathway in the healthy volunteers of Han and Urygur nationalities,in Urumqi.
①There were no significant differences in the antigen levels of TF,t-TFPI,fl-TFPI and in the ratios of TF/t-TFPI,TF/tr-TFPI,tr-TFPI/fl-TFPI between the healthy population of Han and Uygur nationalities. The levels of plasma FⅦAg,FⅦa and FⅦ∶C,D-dimer and the ratios among them were not significantly different.
②The concentration of plasma tr-TFPI and the ratios of TF/fl-TFPI and tr-TFPI/t-TFPI in the Uygur nationality group were markedly lower than those in the Han nationality group.
3) Observation on TFP and other coagulation factors during the onset of acute cerebrocardiac thrombotic diseases.
①Plasma recalcification time in AMI and AIS groups was significantly shorter than that in the control group.
②The levels of TF activity and the concentration of TF and TFPI antigen in plasma were significantly higher in the AMI and AIS groups than those in the control group. But the increament degree of TF was remarkably higher than that of TFPI. Therefore, the TF/TFPI ratio was markedly increasead in the AMI and AIS groups.In contrast to the AMI group,the increament degree of TF activity in plasma was markedly higher in the AIS group.As to TFPI, t-TFPI and fl-TFPI were significantly higher; on the contrary, tr-TFPI was markedly lower than that in the control group.Due to the changes of TF and TFPI, the TF/t-TFPI?TF/tr-TFPI and fl-TFPI/t-TFPI ratios were increased and the TF/fl-TFPI, tr-TFPI/t-TFPI and tr-TFPI/fl-TFPI ratios decreased simultaneously in the AMI and AIS groups compared with the control group.Although the tendency of the changes in most parameters of TFP was consistant in the AMI group and the AIS group,the TF activity in the AIS group was remarkably higher than that in the AMI group.
③Compared with the control group,the levels of plasma FⅦ∶C were remarkably increased in AMI and AIS groups. There was no significant difference in FⅦantigen between the AMI and control groups. The concentration of FⅦa and the ratio of FⅦa/FⅦAg were more remarkably higher in the AMI group, whereas the ratio differences of FⅦa/FⅦ∶C or FⅦ∶C/FⅦAg between the control and AMI groups was not significant. On the other hand, there were no significant differences between AIS and control groups in FⅦa, FⅦAg and FⅦa/FⅦAg ratio. But the FⅦ∶C/FⅦAg ratio was remarkably higher and FⅦa/FⅦ∶C ratio was significantly lower than those in the AIS group.In contrast to the AMI group, FⅦa and the ratio of FⅦa/FⅦ∶C were decreased in the AIS group.
④The levels of plasma D-dimer were remarkably increased in the AMI and AIS groups compared with the control group.
4) Observation on the expression and variation of peripheral monocytes TF-mRNA in patients with AMI and AIS:
①The expression of TF mRNA in human peripheral monocytes was significantly higher in the AMI and AIS groups compared with the control group.
②The levels of TF mRNA expression were positively related to the concentration of plasma TF in the three groups.
Conclusions:
1) The ADI kit used for assay of TFPI concentrations can offer more informations about its types than the Assaypro kit.
2) Compared with the age-matched healthy subjects of Han nationality,there was no significant difference in the ingredients of plasma TFP,but the level of tr-TFPI was remarkably lower in the Uygur nationality.
3) During the onset of AMI and AIS, the initiation of TFP is associated with the thrombotic events.
4) In contrast to the control group,the levels of plasma FⅦ∶C were increased in the AMI and AIS groups;but plasma FⅦa and the ratio of FⅦa/FⅦAg were only elevated in the AMI group.Except TF activity, the tendency of the changes of TFP is consistent in both (AMI and AIS)groups.It may be more sensitive and reliable to use the ratios(such as TF/tr-TFPI,tr-TFPI/fl-TFPI)to evaluate the initiation status of coagulation.
5) The level of D-dimer is considered to be a parameter for the secondary activation of fibrinolysis in patients with AIS and AMI.
6) The expression of TFmRNA in monocytes was upregulated during the onset of AMI and AIS.
引文
[1]李家增.关注动脉血栓性疾病(专论)[J].中华内科杂志, 2006, 45:2-3
[2] Rapaport SI Rao LVM. The tissue factor pathway: How it has become a“prima ballerina”[J]. Thromb Haemost, 1995, 74.:7-17
[3] Gianluca C, Marco V, Paolo F, et al. Tissue factor and cogulation factorⅦlevels during acute myocardial infarction:Association with genotype and adverse events[J]. Arterioscler Thromb Vasc Biol, 2006, 26:2800-2806
[4]贺蓉,贺石林.凝血-抗凝系统与血栓.见刘泽霖?贺石林?李家增主编,血栓性疾病的诊断与治疗[M].北京:人民卫生出版社, 2006, 100
[5] Versteeg HH, Peppelenbosch MP, Spek CA. The pleiotropic effects of tissue factor. a possible role for factorⅦa-induced intracelluar signaling[J]. Thromb Haemost, 2001, 86:1353-1359
[6] Manda’s S K, Pendurthi U R, Rao L V. Cellular localization and trafficking of tissue factor[J]. Blood, 2006, 107:4746-4753
[7] Shebuski RJ, kilgore KS. Role of inflammatory mediators in thrombogenesis[J]. J Pharmacol Exp Ther, 2002, 300:729-735
[8] Pro RT, Sato Y, Mackman N, et al. Mice deficient in tissue factor demonstrate attenuated intimal hyperplasia in response to vascular injury and decreased smooth muscle cell migration[J]. Thromb Haemost, 2004, 92:451-458
[9] Kann KG, Van’t Veer C, Cawthern K, et al. The role of the tissue factor Pathway in initiation of coagulation[J]. Blood Coagul Fibrinolysis, 1998;9 suppl 1:S3-7
[10]贺石林,熊石龙,贺蓉,等. FⅫa受抑稀释凝血活酶试验反映凝血过程的研究[J].中华血液学杂志, 2000, 21:118-121
[11] Savelieva I, BaiPai A, Camm AJ. Stroke in atrial fibrillation:update on Pathophysiology, new antithrombotic therapies, and evolution of Procedures and devices[J]. Ann Med, 2007, 39:371-391
[12] Fredrick R, Pochet L, Charlier C, et al. Modulators of the coagulation cascade:focus and recent advances in inhibitors of tissue factor, factorⅦa and their complex[J]. Curr-Med-Chem, 2005, 12:397-417
[13] Cirillo P, Cali G, Golino P, et al. Tissue factor binding of activated factorⅦtriggers Smoth muscle cell proliferation via extracellular signal-regulated kinase activation[J]. Circulation, 2004, 109:2911-2916
[14] Rao VM, Pendurthi U. Tissue factor-factorⅦa signaling[J]. Arterioscler ThrombVasc Biol, 2005, 25:47-56
[15] Abe Y, Kondo M, Kubota T, et al. Noninvasive assessment of coronary microvascular dysfuntion using TC-99m tetrofosmin SPECT in patients with acute myocardial infarction[J]. J-Nucl-Cardiol, 2004, 11:562-569
[16] Van-der-Putten RF, te-velthuis HT, de-Zwaan C, et al. State and diagnostic value of plasma tissue factor in early-hospitalised patients with chest pain[J]. Br-J-Haematol, 2005, 131:91-99
[17] Meixia He, Zhi bin wen, Xiao fan He, et al. Observation on tissue factor pathway and some other coagulation parameters during the onset of acute cerebrocardiac thrombotic diseases[J]. Thromb Res, 2002, 107:223-228
[18] Bennermo M, Held C, Ericsson CG, et al. Genotype-specific increase in plasma concentrations of activated coagulation factorⅦin response to experimental inflammation. A link between infection and acute myocardial infarction[J]?Thromb Haemost, 2005, 94:427-431
[19]刘伟,综述.组织因子途径抑制物-1与临床疾病的相关性研究[J].国外医学输血及血液学分册, 2004, 27:216-219.
[20] Murray, J, Adams, Jim Thom, et al. The tissue factor pathway in ischemic stroke[J]. Blood Coagulation and Fibrinolysis, 2006, 17:527-532
[21] Golino P, Ravera A, Ragni M, et al. Involvement of tissue factor pathway inhibitor in the coronary circulation of patients with acute coronary syndromes[J]. Circulation 2003, 108:2864-2869
[22] Adama M J, Thom J, Hankey G J, et al. The tissue factor pathway in ischemic stroke[J]. Blood Coagulation and Fibrinolysis, 2006, 17:527-532
[23] Kopp CW, Steiner S, Priglinger U, et al. Parameters of the tissue factor pathway with coumadin/dipyridamole versus ticlopidine as adjunct antithrombotic-drug regimen in coronary artery stenting[J]. Blood Coagul Fibrinolysis 2003, 14:379-386
[24] Sebestjen M, Keber I, Zegura B, et al. Statin and fibrate treatment of combined hyperlipidemia: the effects on some novel risk factors[J]. Thromb Haemost 2004, 92:1129-1135
[25] Bartok A, Steiner S, Seidinger D, et aL. Atorvastatin reduces thrombin generation after percutaneous coronary intervention independent of soluble tissue factor[J]. Thromb Res, 2005, 115:469-474
[26] Kario K, Duell PB, Matsuo T, et aL. High plasma homocysteine levels in elderly Japanese patients are associated with increased cardiovascular disease riskindependently from markers of coagulation activation and endothelial cell damage[J]. Atherosclerosis, 2001, 157:441 -449
[27] Kang WY, Wang HL, Xiong LF, et al. Polymorphisms of the coagulation factorⅦgene and its plasma levels in relation to acute cerebral infarction differences in allelic frequencies between Chinese Han and European populations[J]. Chin Med J (Engl), 2004, 117:71-74
[28] Hirsh J, O’Donnell M, weitz Jl. New anticoagulants[J]. Blood 2005, 105:453-463
[29] Bilgen D, Sonmez H, Ekmekei H, et al. The relationship of TFPI, Lp(a), and oxidized LDL antibody levels in patients with coronary artery disease[J]. Clin Biochem, 2005, 38:92-96
[30] Westrick RJ, Bodary PF, Xu Z, et al. Deficiency of tissue factor pathway inhibitor promotes atherosclerosis and thrombosis in mice[J]. Circulation, 2001, 103:3044-3046
[31] Kato H. Regulation of functions of vascular wall cells by tissue factor pathway inhibitor[J]. Arterioscler Thromb Vasc Biol, 2002, 22:539-548
[32] Lindmark E, Siegbahn A. Tissue fator regulation and cytokine expression in monocyte-endothelial cell co-culturee:effects of a statin, an ACE-inhibitor and a Low-molecular-weight heparin[J]. Thromb Res, 2002, 108:77-84
[33] Piro O, Broge GJ Jr. Comparison of cell-surface TFPIαandβ[J]. J Thromb Haemost, 2005, 3:2677-2683
[34] Lisowski P, Malyszko J, Lisowska A, et al. Role of the hemostatic system in pathogenesis of atherosclerosis as the main etiology of coronary ischemia[J]. Pol Merkuriusz Lek, 2004, 16:465-467
[35]戴宇翔,张抒扬.组织因子和其途径抑制物在冠状动脉疾病及治疗中的作用[J].中华内科杂志, 2005, 44:866-868
[36] Makin AJ, Blann AD, chung N A, et al. Assessment of endothelial damage in atherosclerotic vascular disease by quantification of circulating endothelial cells. Relationship with von willebrand factor and tissue factor[J]. Eur-Heart-J, 2004, 25:371-376
[37] Eilertsen KE, Osterud B. Tissue factor: (patho) physiology and cellular bilolgy[J]. Blood Coagul Fibrinolysis, 2004, 15:521-538
[38] Bochkov VN, Mechtcherinkova D, Lucerna M, et al. Oxidized phospholipids stimulate tissue factor expression in human endothelial cells via activation of EPF/EGR-1 and Ca++/NFAT[J]. Blood, 2002, 99:199-206
[39] Corti R, Hutter R, Badimon JJ, et al. Evolving concepts in the triad of atherosclerosis, inflammation and thrombosis[J]. J Thromb Thrombolysis, 2004, 17:35-44
[40] Moons AH, Levi M, Peters RJ. Tissue factor and coronary artery disease[J]. Cardiovasc Res, 2002, 53:313-325
[41] Banai S, Gertz SD. Tissue factor as therapeutic target in coronary syndromes[J]. Am J cardiol, 2001, 87:763-765
[42] Ardissino D, Merlini PA, Arlens R, et al. Tissue factor in human coronary atherosclerotic plaques[J]. Clin Chim Acta, 2000, 219:235-240
[43] Maier W, Altwegg LA, Corti R. Inflammatory markers at the site of ruptured plaque in acute myocardia infarction: locally increased interleukin-6 and serum amyloid a but decreased C-reactive protein[J]. Circulation, 2005, 111:1355-1361.
[44] Moreno PR, Palacios IF, Leon MN, et al. Histopathologic comparison of human coronary in-stent and post-balloon angioplasty restenotic tissue[J]. Am J Cardiol, 1999, 84:462-466
[45] Ott I, Andrassy M, Zieglgansberger D, et al. Regulation of monocyte procoaguloant activity in acute myocardial infarction:role of tissue factor and tissue factor pathway inhibitor-1[J]. Blood, 2001, 97:3721-3726
[46] Steffel J, Iseli S, Arnet C, et al. Cocaine unbalances endothelial tissue factor and tissue factor pathway inhibitor expression[J]. J Mol Cell Cardiol, 2006, 40:746-749
[47] Saigo M, Abe S, Ogawa M, et al. Imbalance of plasm inogen activator inhibitor-1/tissue plasm inogen activator and tissue factor/tissue factor pathway inhibitor in young Japanese men with myocardial infarction[J]. Tromb Haemost, 2001, 86:1197-1203
[48] Malarstig A, Tenno T, Johnston N, et al. Genetic variations in the tissue factor gene are associated with clinical outcome in acute coronary syndrome and expression levels in human monocytes[J]. Arterioscler Thromb Vasc Biol, 2005, 25:2667-2672
[49] Dahm A, Van Hylckama Vlieg A, Bendz B, et al. Low levels of tissue factor pathway inhibitor (TFPI) increase the risk of venous thrombosis[J]. Blood, 2003, 101:4387-4392
[50] Mizuno O, Ikeda U, Hojo Y et al. Tissue factor expression in coronary circulation as a prognostic factor for late restenosis after coronary angioplasty[J]. Cardiology, 2001, 95:84-89
[51] Ott I, koch W, Von Beckerath N, et al. Tissue factor promotor polymorpnism-603A/G is associated with myocardial infarction[J]. Atherosclerosis, 2004, 177:189-191
[52]胡豫,徐丹梅,孙春艳.缺血性心脏病患者血浆凝血因子Ⅶ与血脂的关系[J].中华内科杂志, 2005, 44:418-420
[53]刘敏娟,周立红,刘世明,等.血浆凝血因子Ⅶ测定在冠心病中的临床意义[J].临床心血管病杂志, 2000, 16:443-444
[54] Di Castelnuovo A, D’Orazio A, Amore C, et al. The decanucleotide insertion deletion polymorphism in the promoter region of the coagulation factorⅦgene and the risk of familial myocardial infarction[J]. Thromb Res, 2000, 98:9-17
[55]康文英,王鸿利,熊立凡,等.冠心病患者血浆凝血因子Ⅶ水平及其基因多态性研究[J].中华血液学杂志, 2002, 23:457-459
[56] Petrovic D, Zorc M, Keber I, et al. Joint effect of G1691 A factor V pointmutation and factorⅦA rg/Gln(353) gene polym orphism on the risk of premature coronary artery disease[J]. Ann Genet, 2001, 44:33-36
[57]徐耕,金国栋,傅国胜,等.凝血因子V和Ⅶ基因多态性与冠心病的初步研究[J].中华医学遗传学杂志, 2003, 20:39-42
[58]宋善俊,夏凌辉.冠状动脉缺血性心脏病与血栓形成.见:王振义,李家增,阮长耿,主编.血栓与止血基础理论与临床[M].上海:上海科学技术出版社, 2004, 529-543
[59] Jander S, sitzer M, wendt A, et al. Expression of tissue factor in high-grade carotid artery stenosis: association with plaque destabilization[J]. stroke, 2001, 32:850-854
[60] Klein BD, White HS, Callahan KS. Cytokine and intracellular signaling regulation of tissue factor expression in astrocytes[J]. Neurochem Int, 2000, 36:441-449
[61] Duering C, Kosch A, Langer C, et al. TFPI is an independent risk factor for thromboembolism and stroke[J]. Thromb Haemost, 2004, 92:707-712
[62]刘立根,段磊,朱宏钧等,腔隙性和动脉粥样硬化性脑梗死急性期患者血浆组织因子的检测[J].中华血液学杂志, 2002, 23:488-489
[63] Zhang X, Xu Y, Hong M, et al. Plasma thrombomodulin, fibrinogen, and activity of tissue factor as risk factor for acute cerebral infarction[J]. Am J Clin Pathol, 2007, 128:287-292
[64]刘泽霖.血栓病的分类?发病机制及危险因素.见刘泽霖?贺石林?李家增主编.血栓性疾病的诊断与治疗[M].北京:人民卫生出版社, 2006, 15
[65]潘学谊,丁彩屏,商谊.血浆凝血因子活性测定在急性缺血性脑卒中的临床研究[J].血栓与止血学, 2004, 10:119-122
[66] Scarabin PY, Aillaud MF, Amouyel P, et al. Associations of fibrinogen, factorⅦand PAI-1 with baseline findings among 10, 500 male participants in a prospective studyof myocadial infarction-the PRIME study. Prospective epidemiological study of myocardial infarction[J]. Thromb Haemost, 1998, 80:749-756
[67]康文英,王鸿利,熊立凡,等.脑梗死病人血浆凝血因子Ⅶ水平及其基因多态性研究[J].诊断学理论与实践, 2002, 1:79-81
[68] Pinotti M, Toso R, Girelli D, et al. Modulation of factorⅦlevels by intron 7 polymorphisms:population and in vitro studies[J]. Blood, 2000, 95:3423-3428
[69] Albers GW. Antithrombotic therapy for prevention and treatment of ischemic stroke[J]. J Thromb Thrombolysis, 2001, 12:19-22
[70] Sacco RL, Adams R, Albers G, et al. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack:a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke:Cosponsored by the Council on cardiovascular radiology and intervention:the American Acedemy of Neurology affirms the value of this guideline[J]. Stroke, 2006, 37:577-617
[71]他汀类药物预防缺血性卒中/短暂性脑缺血发作专家组.他汀类药物预防缺血性卒中/短暂性脑缺血发作的专家建议[J].中华内科杂志, 2007, 46:81-82
[72] Shebuski RJ, kilgore KS. Role of inflammatory mediators in thrombogenesis[J]. J Pharmacol Exp Ther, 2002, 300:729-735
[73] Egorina E M, Sovershaev M A, Osterud B. In-cell Western assay:a new approach to visualize tissue factor in human monocytes[J]. J-Thromb-Haemost, 2006, 4:614-620
[74] Sase T, wada H, KamiKura Y, et al. Tissue factor messenger RNA levels in leukocytes compared with tissue factor antigens in plasma from patients in hypercoagulable state caused by various diseases[J]. Thromb-Haemost, 2004, 92:132-139
[75] Buchs A E, kornberg A, Zahavi M, et al. Increased expression of tissue factor and receptor for advanced glycation end products in peripheral blood mononuclear cells of patients with type II diabetes mellitus with vascular complications[J]. Exp–Diabesity-Res. 2004, 5:163-169
[76] Meixia He, xiao fan He, Qin zhi Xie, et al. Angiotensin II induces the expression of tissue factor and its mechanism in human monocytes[J]. Thrombosis Research, 2006, 117:579-590
[77] Bai-H, Ma-D, Zhang-Y-G, et al. Molecular design and characterization of recombinant long half-life mutants of human tissue factor pathway inhibitor[J]. Thromb-Haemost, 2005, 93:1055-1060
[78] Lupu-C, Hu-X, Lupu-F. Caveolin-1 enhances tissue factor pathway inhibitor exposure and function on the cell surface[J]. J-Biol-Chem, 2005, 280:22308-22317
[79] Audu-P, Nielsen-V-G, Armstead-V, et al. The impact of tissue factor pathway inhibitor on coagulation kinetics determined by thrombelastography[J]. Anesth-Analg, 2006, 103:841-845
[80] Hedner U, Erhardtsen E. Future possibilities in the regulation of the extrinsic pathway:rFⅦa and TFPI[J]. Ann Med, 2002, 32 Suppl 1:68-72
[81] Gerlach R, Scheuer T, Bohm M, et al. Increased levels of plasma tissue factor pathway inhibitor in patients with glioblastoma and intracerebral metastases[J]. Neurol Res, 2003, 25:335-338
[82] Yin X, Yutanin C, Ikeda Y, et al. Tissue factor pathway inhibitor gene delivery using HVJ-AVE liposmes markedly reduces restenosis on atherosclerotic artheries[J]. Cardiovase Res, 2002, 56:454-463
[83] Nishioka T, Yokota M, Hino M, et al. Tissue factor pathway inhibitor can interact with platelets[J]. J Immunol Methods, 2002, 266:181-184
[84] Shimokawa T, Yamamoto K, Kojima T, et al. Down-regulation of murine tissue factor pathway inhibitor mRNA by endotoxin and tumor necrosis factor-alpha in vitro and in vivo [J]. Thromb Res, 2000 ; 100:211-221
[85] Uszynski M, Zekanowska E, Uszynski W, et al. Tissue factor(TF) and tissue factor pathway inhibitor(TFPI)in amniotic fluid and blood plasma:implications for the mechanism of amniotic fluid embolism [J]. Eur J Obstet Gynecol Reprod Biol, 2001,95:163-166
[86] Zemanova P, Opatrny K, Vit L, et al. Tissue factor, its inhibitor, and the thrombogenicity of two new synthetic membranes [J]. Artificial Organs, 2005, 29:651-657
[87] Creasey A A, Reinhart K. Tissue factor pathway inhibitor activity in sevre sepsis [J]. Crit Care Med, 2001,29:126-129
[88] Lwaleed B. A, Bass PS. Tissue factor pathway inhibitor:structure, biology and involvement in disease[J]. J-Pathol, 2006, 208:327-339
[89] Morange PE, Simon C, Alessi MC, et al. Endothelial cell markers and the risk of coronary heart disease: the prospective epidemiological study of myocardial infarction (PRIME) study[J]. Circulation, 2004, 109:1343-1348
[90] Brodin E, Borvik T, Sandset PM, et al. Infarction (MI)-a population-based case-cortrol study[J]. Thromb-Haemost, 2004, 92:178-184
[91] Sandset PM, In:Jespersen J, Bertina, RM, et al. Laboratory techniques in thrombosis-a manual [J]. Dordrecht: Kluwer Academic Publishers BV, 1999,171-181
[92] Ariens RA, Alberio G, Moia M, et al. Low levels of heparin-releasable tissue factor pathway inhibitor in young patients with thrombosis [J]. Thromb Haemost 1999,81:203-207
[93] Kemona-chetnik I, Bodzenta-Lukaszyk A. Kucharewicz I, et al. Tissue factor and tissue factor pathway inhibitor during specific bronchial challenge in allergic asthma patients[J]. Przegl Lek, 2005, 62:98-101
[94]贺石林,李俊成,秦晓群主编.临床生理学[M],北京,科学出版社2001, 138-147
[95]李家增,王鸿利,韩忠朝主编.血液实验学[M],上海科学技术出版社, 1997, 378-380
[96] Hackeng TM, Sere KM, Tans G, et al. Protein s stimulates inhibition of the tissue factor pathway by tissue factor pathway inhibitor[J]. Proc-Natl-Acad-Sci-U-S-A, 2006, 103:3106-3111
[97] Steppich B, Mattisek C, sobczyk D, et al. Tissue factor pathway inhibitor on circulating microparticles in acute myocardial infarction[J]. Thromb Haemost, 2005, 93:35-39
[98] Kaiser B, Hoppensteadt DA, Fareed J. Tissue factor pathway inhibitor: an update of potential implications in the treatment of cardiovascular disorders[J]. Expert Opin Investig Drugs, 2001,10:1925-1935
[99] Keller TT, Nagle C, Te-Velthuis H, et al. Tissue factor serum Levels and the risk of future coronary artery disease in apparenty healthy men and women:the EPIC-Norfolk prospective population study[J]. J-Thromb-Haemost, 2006, 4:2391-2396
[100]Ardissino D, Merlini PA, Bauer KA, et al. Thrombogenic potential of human coronary atherosclerotic plaques[J]. Blood, 2001, 98:2726-2729
[101]王鸿利.凝血因子筛选试验;王鸿利.凝血因子功能活性检测;汉建忠,等.凝血因子激活标志物检测;邵慧珍.纤溶降解产物检测方法.见李家增,王鸿利,韩中朝主编.血液实验学[M].上海,上海科学技术出版社, 1997, 345-428
[102]王学峰.凝血系统的实验室检查;凝血因子的实验室检查.见王振义,李家增,阮长耿主编.血栓与止血基础理论与临床[M].上海,上海科学技术出版社, 2004, 903-914
[103]文志斌,熊石龙,何晓凡,等.急性脑梗死发作期间组织因子途径改变的观察[J].中国危重病急救医学, 2003, 9:529-531
[104]刘敏娟,周立红,董临江,等.血浆凝血因子Ⅶ测定在缺血性心脑血管病中的临床意义[J].中华血液学杂志, 2000, 3:152-153
[105]窦红菊,胡钧培,邹丽芳,等.急性脑梗死患者血栓前体蛋白凝血酶抗凝血酶复合物和D-二聚体的检测及其临床意义[J].血栓与止血学, 2004, 3:115-116
[106]陈南,华守明,卢辉和,等. D-二聚体与纤维蛋白质在冠心病中的临床意义[J].中国微循环, 2006, 10:143-145
[107]Song KS, Kim HK. Plasma levels of tissue factor antigen in patients with non-insulin-dependent diabetes mellitus[J]. Yonsei Med J, 2004, 45:38-42
[108]陈敏.血脂水平与脑梗死的关系[J].上海医学, 2004, 10:772-773
[109]Kural BV. Orem C. Uydu HA, et al. The effects of lipid-lowering therapy on paraoxonase activities and their relationships with the oxidant-antioxidant system in patients with dyslipidemia[J]. Coron Artery Dis, 2004,15:277-283
[110]祁燕,谢自敬,阿不力克木.乌鲁木齐市维吾尔族成年人代谢综合征流行病学调查[J].中国现代医学杂志, 2004, 19:155-156
[111]曾小云,谢自敬,伊力哈木.乌鲁木齐市维吾尔族成年人超重和肥胖的流行病学调查[J].中国临床康复, 2005, 3:17-19
[112]王薇彬,李云,谢自敬,等.乌鲁木齐维吾尔族居民1002人糖?脂代谢紊乱与胰岛素抵抗的关系[J].中国临床康复, 2004,33:7418-7419
[113]Passi SJ. Manchanda SC. Lakshmi R, et al. Blood lipid and glucose levels of adolescents belonging to upper income group as markers for assessing the risk of CAD/DM[J]. Asia Pac J Clin Nutr, 2004,13(suppl):s104
[114]许建平.病因与发病机制.见:刘泽霖,贺石林,李家增主编.血栓性疾病的诊断与治疗[M].北京:人民卫生出版社, 2000, 18-25
[115]Lacoviello L, Di Castelnuovo A, De Knijff P, et al. Polymorphisms in the coagulation factorⅦgene and risk of myocardial infarction[J]. N Engl J Med, 1998, 338:79-85
[116]Sato Y, Hatakeyama K, Yamashita A, et al. Proportion of fibrin and platelets differs in thrombi on ruptured and eroded coronary atherosclerotic plaques in humans[J]. Heart, 2005, 91:526-530
[117]Seljeflot I, Hurlen M, Arnesen H. Increased levels of soluble tissue factor during long-term treatment with warfarin in patients after an acute myocardial infarction[J]. J Thromb Haemost, 2004, 2:726-730
[118]Xu G, Jin G, Fu G, et al. Polymorphisma in the coagulation factorⅦgene and risk of myocardial infarction in patients undergoing coronary angiography[J]. Chin Med J, 2003, 116:1194-1197
[119]Cai Q, Chen J, Ma H, et al. Association of coagulation factorⅦwith the risk of myocardial infarction in Chinese[J]. Chin Med J, 2000, 113:1059-1063
[120]Roldan V, Marin F, Fernandez, et al. Tissue factor /tissue factor pathway inhibitor system and long-term prognosis after acute myocardial infarction[J]. Int J Cardiol, 2001, 78:115-119
[121]Cote R, Wolfson C, Solymoss S, et al. Hemostatic markers in patients at risk of cerebral ischemia[J]. Stroke, 2000, 31:1856-1862
[122]刘泽霖,贺石林,李家增主编.血栓性疾病的诊断与治疗[M].北京:人民卫生出版社, 2000, 18-25
[123]Reganon E, Vila V, Martinez-sales V, et al. Association between inflammation and hemostatic markers in atherothrombotic stroke[J]. Thromb Res, 2003, 112:217-221
[124]Morrissey JH. Tissue factor: A key molecule in hemostatic and nonhemostatic systems[J]. Int J Hematol, 2004, 79:103-108
[125]Tilley R, Mackman N. Tissue factor in hemostasis and thrombosis[J]. Semin-Thromb-Hemost, 2006, 32:5-10
[126]Falciani M, Gori AM, Fedi S, Chiarugi, et al. Elevated tissue factor and tissue factor pathway inhibitor circulating levels in ischaemic heart disease patients[J]. Thromb Haemost, 1998,79:495-9
[127]Freeburn JC, Wallace JM, Strain JJ, et al. Monocyte tissue factor-like activity in post myocardial infarction patients[J]. Br J Haematol, 1998,102:605-8
[128]许建平,曹燕娜,文志斌,等.急性心脑血管血栓性疾病患者血浆FⅦ∶C?FⅧ:C?凝血酶原及纤维蛋白原的变化[J].血栓与止血学, 2001, 7:53-56
[129]Dicastelnuovo A, D’Orazio A, Amore C, et al. The decanucleotide insertion/deletion polymorphism in the promoter region of the coagulation factorⅦgene and the risk of familial myocardial infarction[J]. Thromb Res, 2000, 98:9-17
[130]Osterud B, Bjorklid E. Sources of tissue factor[J]. Semin-Thromb-Hemost, 2006, 32:11-23
[131]Halim A G, Hamidon B B, Cheong S k, et al. The prognostic value of tissue factor levels in acute ischaemic stroke[J]. Singapore Med J, 2006,47:400-403
[132]Leatham EM, Math PMW, Tooze JA, et al. Increased monocytes tissue factor expression in coronary disease[J]. Br Heart J, 1995, 73:10-13
[133]Letter to the Editors-in-chief. Tissue factor and tissue factor pathway inhibitor levels in coronary artery disease:correlation with the severity of atheromatosis [J]. Thrombosis Research, 2007, 04, 013
[134]Falciani M, Gori AM, Fedi S, et al. Elevated tissue factor and tissue factor pathway inhibitor circulating levels in ischaemic heart disease patients[J]. Thromb Haemost, 1998, 79:495-499
[135]王学锋,王鸿利主编.血栓与止血的检测及应用[M].上海:上海世界图书出版公司, 2002, 417-422
[136]Mayer TE, Hamann GF, Brueclcmann HJ. Treatment of basilar artery embolism with a mechanical extraction device:necessity of flow reversal[J]. Stroke, 2002, 33:2232-2236
[137]Shiozaki T, Nakajima Y, Taneda M, et al. Efficacy of moderate hypothermia in patients with severe head injury and intracranial hypertension refractory to mild hypothermia[J]. J Neurosurg, 2003, 99:47-51
[138]Krupinski J, Turu MM, Font Ma, et al. Blood-borne tissue factor activity perdicts major cerebrovascular events in patients undergoing carotid enderterectomy. Result from a 1-year follow-up study[J]. Cerebrovasc Dis, 2008, 25:32-39
[139]王立军.凝血因子Ⅶ研究进展[J].血栓与止血杂志, 2002. 8:42-43
[140]Kraaijenhagen RA, in`t-Anker PS, Koopman MM, et al. High plasma concentration of factorⅦC is a major risk factor for venous thromboembolism[J]. Thromb Haemost, 2000, 83: 5-9
[141]Aron R, Folson, Nend Aleksic. Prospective study of fibrinolytic factors and incident coronary heart disease[J]. Arterioscler Thromb Vasc Biol, 2001, 21:611-613
[142]Mark Barber. Peter Langhorne, Ann Rumley, et al. Hemostatic function and progressing ischemic stroke D-dimer predicts early clinical progression[J]. Stroke, 2004, 35:1421-1425
[143]Ottani F, Galvani M. Prognostic role of hemostatic markers in acute coronary syndromes patients [J]. Clin Chim Acta, 2001, 311:33-39
[144]Li Feng, Zhang Guibin, zhao Wen zhou. Coagulation and fibrinolytic avtivity in patients with acute cerebral infarction[J]. Chin Med J, 2003, 116:475-477
[145]张小平,胡豫,杨焰,等.脑梗死与血浆D-二聚体/纤维蛋白原比值的关系[J].临床血液学杂志, 2006, 19:216-217
[146]Christersson C, Oldgren J, Bylock A, et al. Early decrease in coagulation activity after myocardial infarction is associated with lower risk of new ischaemicevents:observations from the ESTEEM Trial[J]. Eur Heart J, 2007, 28:692-698
[147]夏大胜,综述.组织因子与冠心病[J].中国心血管杂志, 2003, 8:294-297
[148]Jan steffel MD, Thomas F, Luscher MD, et al. Tissue factor in cardiovascular diseases molecular mechanisms and clinical implications[J]. Circulation, 2006, 113:722-731
[149]Matezky S, Tani S, Kangavari S, et al. Smoking increases tissue factor expression in atherosclerotic plaques: Implications for plaques thrombogenicity[J]. Circulation, 2000, 102:602-604
[150]姜德谦,黄秋霞,王俊,等.高甘油三酯冠心病患者血浆凝血因子ⅦC活性研究[J].临床心血管病杂志, 2003, 19:205-206
[151]Viswambharan H. Ming XF. Zhu S. et al. Reconstituted high-density lipoprotein inhibits thrombin-induced endothelial tissue factor expression through inhibition of RhoA and stimulation of phosphatidylinositol 3-kinase but not Akt/endothelial nitric oxide synthase[J]. Circ Res, 2004, 94:918-925
[152]Sambola A, Osende J, Hathcock J, et al. Role of risk factors in the modulation of tissue factor activity and blood thrombogenicity[J]. Circulation, 2003, 107:973-977.
[153]Lim HS, Blann A D, Lip Gy. Soluble CD40 ligand, soluble P-selectin, interleukin-6, and tissue factor in diabetes mellitus: relationships to cardiovascular disease and risk factor intervention[J]. Circulation, 2004, 109:2524-2528.
[154]E to M, Kozai T, Cosention F, et al. Statin prevents tissue factor expression in human endothelial cells: role of Rho/Rho-kinase and Akt pathways[J]. Circulation, 2002, 105:1756-1759.
[155]Brandes RP, Beer S, Ha T, et al. Withdrawal of cerivastatin induces monocyte chemoattractant protein 1 and tissue factor expression in cultured vascular smooth muscle cells[J]. Arterioscler Thromb Vasc Biol, 2003, 23:1794-1800.
[156]Morel O, Toti F, Hugel B, et al. Cellular microparticles:a disseminated storage pool of bioactive vascular effectors[J]. Curr Opin Hematol, 2004, 11:156-164.
[157]Meisel SR, Xu XP, Edgington TS, et al. Differentiation of adherent human monocytes into macrophages markedly enhances tissue factor protein expression and procoagulant activity [J]. Atherosclerosis, 2002, 161:35-43
[158]Becker BF, Heindl B, Kupatt C, et al. Monocyte-endothelial cell and hemostasis[J]. Z Kardiol, 2000, 89:160-167
[159]Kim HK, Song KS, Park YS, et al. Changes of plasma tissue factor and tissue factor pathway inhibitor antigen levels and induction of tissue factor expression onmonocytes in coronary artery disease[J]. Cardiology 2000, 93:31-36.
[160]王蕊,温丙昭,马依彤.急性心肌梗死患者组织因子途径比值改变及其意义[J].中华内科杂志, 2007, 46:762-763.
[161]黄细莲,陈方平.血细胞源性组织因子的研究现状[J].中华内科杂志, 2007, 46:74-75.
[162]Falk E, Fernandez-Ortiz A. Role of thrombosis in atherosclerosis and its complications[J]. Am J Cardiol, 1995, 75:3B-11B
[163]Moreno PR, Palacios IF, Leon MN, et al. Histopathologic comparison of human coromary in-stent and post-balloon angioplasty restenotic tissue[J]. Am J Cardiol, 1999, 84:462-466
[164]Biro E, Sturk-Maquelin KN, Vogel GM, et al. Human cellderived microparticles promote thrombus formation in vivo in a tissue factor-dependent manner[J]. J Thromb Haemost, 2003, 1:2561-2568
[165]Diamant M, Tushuizen ME, Sturk A, et al. Cellular microparticles:new players in the field of vascular disease[J]? Eur J Clin Invest, 2004, 34:392-401
[166]Mackman N, Tilley RE, Key NS. Role of the extrinsic pathway of blood coagulation in hemostasis and thrombosis[J]. Arterioscler Thromb Vasc Biol, 2007, 27:1687-1693
[167]Qsterud B, Bjorklid E. Sources of tissue factor[J]. Semin Thromb Hemost, 2006, 32:11-23
[168]Egorina EM, Swvershaev MA, Bjorkoy G, et al. Intracellular and surface distribution of monocyte tissue factor application to inersubject variability[J]. Arterioscler Thromb Vasc Biol, 2005, 25:1493-1498.
[169]Aras O, Shet A, Bach RR et, al. Induction of microparticle and cell-associated intrvascular tissue factor in human endotoxemia[J]. Blood, 2004, 193:4545-4553.
[170]马琦琳,杨天伦,孙明,等.胰岛素样生长因子-1对内皮细胞活力及组织因子的影响[J].中华血液学杂志, 2007, 28:605-608
[171]Meixia He, Xiaofan He, Qinzhi xie, et al. Angiotensin II induces the expression of tissue factor and its mechanism in human monocytes[J]. Thrombosis Research, 2005, 4:1-11.
[172]Mueller J, Rox JM, Madlener K. Quantitative tissue factor gene expression analysis in whole blood:development and evaluation of a real-time PCR platform[J]. Clin Chem, 2004, 50:245-247
[173]Ozcan M, Morton CT, Solovey A, et al. Whole blood tissue factor procoagulantactivity remains detectable during severe aplasia following bone marrow and periphera blood stem cell transplantation[J]. Thromb Haemost, 2001, 85:250-255
[174]Santucci RA, Ercich J, Larriola J, et al. Measurement of tissue factor activity in whole blood[J]. Thromb Haemost, 2000, 83:445-454
[175]Marsik C, Quehenberger P, Mackman N, et al. Validation of a novel tissue factor assay in experimental human endotoxemia[J]. Thromb Res, 2003, 111:311-315
[176]Muller I, Klocke A, Alex M, et al. Intravascular tissue factor initiates coagulation via circulating microvesicles and platelets[J]. FASEB J, 2003, 17:476-478
[177]Steffel J, Thomas F. Tissue factor in cardiovascular diseases molecular mechanisms and clinical implications[J]. Circulation, 2006, 113: 722-731.
[1] Versteeg HH, Ruf W. Emerging insights in tissue factor-dependent signaling events[J]. Semin-Thromb-Hemost, 2006, 32:24-32
[2] Golino P, Cirillo P, Ragni M, et al. Expression of exogenous tissue factor pathway inhibitor in vivo suppresses thrombus formation in injured rabbit carotid arteries[J]. J Am Coll Cardiol, 2001, 38:569-576
[3] Lwaleed BA, Bass PS. Tissue factor pathway inhibitor: structure, bilolgy and involvement in disease[J]. J Pathol, 2006, 208: 327~339
[4] Xu-C, Hu-Xu-X, Zeng-Y, et al. Simulation of a mathematical model of the role of the TFPI in the extrinsic Pathway of Coagulation[J]. Comput-Biol-Med, 2005, 35:435-445
[5]宋善俊?夏凌辉.冠状动脉缺血性心脏病与血栓形成.见王振义?李家增,阮长耿等主编.血栓与止血基础理论与临床[M].上海:上海科学技术出版社, 2004, 529-544
[6] Dusse LM, Carvalho MG, Cooper AJ, et al. Tissue factor and tissue factor Pathway inhibitor:a potential role in Pregnancy and obsteric vascular complications[J]. Clin-chim-Acta, 2006, 372:43-46
[7] Mackman N. Alternativaly spliced tissue factor-one cut too many[J]. Thromb Haemost, 2007, 97:5-8
[8]Siegbahn A, Johnell M, Sorensen BB, et al. Regulation of chemotaxis by the cytoplasmic domain of tissue factor[J]. Thromb Haemost, 2005, 93:27-34
[9]Szotwski B, Antoniak S, Rauch U. Alternatively spliced tissue factor:a previously unknown piece in the puzzle of hemostasis[J]. Trends Cardiovasc Med, 2006, 16:177-182
[10]Bogdowov V Y,Balasubramanian V,Hathcock J,et al.Alternatively spliced human tissue factor:a circulating soluble,thrombogenic protein[J].Nature Medicine, 2003,9:458-462
[11]Szotowski B,Antoniak S,Pollen W,et al.Procoagulant soluble tissue factor is released from endothelial cells in response to inflammatory cytokines[J].Circ Res,2005,96:1233-1239
[12]Censarek P, Bobbe A, Grandoch M, et al. Alternatively spliced human tissue factor(asHTF) is not pro-coagulant[J]. Taemost, 2007, 97:11-14
[13]Eilertsen KE, Osterud B, Tissue factor:(patho)physiology and cellular biology[J].Blood Coagul Fibrinolysis, 2004, 15:521~538
[14]:Golino P, Cimmino G. Targenting tissue factor as an antithrombotic strategy[J]. Semin Vasc Med, 2003, 3:205-214
[15]Llorente-cortes V, Otero-Vinas M, Camino-Lopez S, et al. Aggregated low-density lipoprotein uptake induces membrane tissue factor Procoagulant activity and microparticle release in human vascular smooth muscle cells[J]. Circulation, 2004, 110:452-459
[16]Chou J, Mackman N, Merrill-Skoloff G, et al. Hematopoietic cell-derived microparticle tissue factor contributes to fibin formation during thrombus propagation[J]. Blood, 2004, 104:3190-3197
[17]Day SM, Reeve JT, Pedersen B, et al. Macrovascular thrombosis is driven by tissue factor derived primarily from the blood vessel wall[J]. Blood, 2005, 105:192-198
[18]Morrissey TH. Clotting hits the wall[J]. Blood, 2005, 105:3-4
[19]Butenas S, Bouchard BA, Brummel-ziedins KE, et al. Tissue factor activity in whole blood[J]. Blood, 2005, 105:2764-2770
[20]黄细莲,陈方平,杜建伟,等.血栓性疾病血小板相关组织因子水平及活性的改变化及意义[J].中华内科杂志, 2005, 8:216-218
[21] Aagaard S, Hjordal VE, Barker JH. The efficacy of tissue factor pathway inhibitor (TFPI) as topically applied antithrombotic agent[J]. APMIS Suppl, 2003: 102-107
[22]Dahm AE, Andersen TO, Rosendaal F, et al. A novel anticoagulant activity assay of tissue factor pathway inhibitor(TFPI) [J]. J Thromb Haemost, 2005, 3:651-658
[23]Piro O,Broge GJ.Jr.Comparison of cell-surface TFPIαandβ[J].J Thromb Haemost 2005,3:2677-2683
[24]Jayachandran M, Sanzo A, Owen WG, Miller VM. Estrogenic regulation of tissue factor and tissue factor pathway inhibitor in platelets[J]. Am J Physiol Heart Circ Physiol, 2005, 289: H1908 -1916
[25]Becker RC, Alexander JH, Li Y, Robertson T, et al. Vascular endothelial tissue factor pathway inhibitor kinetics in culture following exposure to DX-9065a—a selective and direct factor Xa inhibitor[J]. J Thromb Thrombolysis, 2004, 18:193-197.
[26] Ndonwi M, Broze G Jr, Bajaj SP. The first epidermal growth factor-like domains of factor Xa and factorⅨa are important for the activation of the factorⅦ—tissue factor complex[J]. Thromb Haemost, 2005, 3:112-118
[27]Brodin E, Iversen N, Hansen JB. Impact of native VLDL on tissue factor pathway inhibitor in endotheliai cells and interactions between TFPIand lipoprotein lipase[J]. JLab Clin Med, 2006, 147:167-173
[28]Walker CP, Royston D. Thrombin generation and its inhibition:a review of the scientific basis and mechanism of action of anticoagulant therapies[J]. Br J A Naesth, 2002, 88:848-863
[29]Sierko E, Zauadzki RJ, Wojtukiewicdz MZ. Tissue factor pathway inhibitors[J]. Pol Merkuriusz Lek, 2002, 13:66-69
[30]Jude B, Zawadzki C, Susen S, et al. Relevance of tissue factor in cardiovascular disease[J]. Arch Mal Coeur Vaiss, 2005, 98:667-671
[31]Marutsuka K, Hatakeyama K, Yamashita A, et al. Role of thrombogenic factors in the development of atherosclerosis[J]. J Atheroscler Thromb, 2005, 12:1-8
[32]Cozzi E, Wingard C J, Cascio W E, et al. Effect of ambient particulate matter exposure on hemostasis[J]. Translational Research, 2007, 149:324-332
[33]Moreno PR. Pathophysiology of plaque disruption and thrombosis in acute ischemic syndromes[J]. J Stroke Cerebrovasc Dis, 2001, 10(2 pt 2):2-9
[34]Moons AH, Levi M, Peters R J, Tissue factor and coronary artery disease[J]. Cardiovasc Res, 2002, 53:313-325
[35]Dahm A, Van Hylckama Vlieg A, Bendz B, et al. Low levels of tissue factor pathway inhibitor (TFPI) increase the risk of venous thrombosis[J]. Blood, 2003, 101:4387-4392
[36]Porta B, Baldassarre D, Camera M, et al. E-selectin and TFPI are associated with carotid intima-media thickness in stable IHD patients:The baseline findings of the MIAMI study[J]. Nutr Metab Cardiovasc Dis, 2007, 20;[Epub ahead of print]
[37]Al-Nozha MM, Abdel–Gader AG, Arafah MR, et al. Tissue factor pathway inhibitor, natural coagulation inhibitors and hemostatic activation markers in patients with acute coronary syndromes[J]. Saudi Med J, 2005, 26:937-942
[38]Kopp CW, Holzenbein T, Steiner S, et al. Inhibition of restenosis by tissue factor pathway inhibitor: in vivo and in vitro evidence for suppressed monocyte chemoattraction and reduced gelatinolytic activity[J]. Blood, 2004, 103:1653-1661
[39]Lwaleed BA, Bass PS. Tissue factor pathway inhibitor:structure, biology and involvement in disease[J]. J Phatol, 2006, 208:327-339
[40]Ott I, koch W, Von Beckerath N, et al. Tissue factor promotor polymorpnism-603A/G is associated with myocardial infarction[J]. Atherosclerosis, 2004, 177:189-191
[41]Liu M, Wu B, Wang WZ, et al. Stroke in China: epidemiology, prevention, and management stategids[J]. Lancet Neurol, 2007, 6: 456-464
[42]Charles W, Cathie S, Martin D et al. Stroke[J]. Lancet, 2003, 362: 1211-1224
[43]Wen ZB, Xiong SL, He XF, et al. Observation on tissue factor pathway during the onset of acute cerebral infarction[J]. Zhongguo Wei Zhong Bing JI Jiu Yi Xue, 2003, 15:529-531
[44]Hassan A, Hunt BJ, O`sullivan M, et al. Markers of endothelial dysfunction in lacunar infarction and ischaemic leukoaraiosis [J]. Brain, 2003, 126 (pt2): 424-432
[45]Casas JP, Hingorani AD, Bautista LE, et al. Meta-analysis of genetic studies in ischemic stroke: thirty-two genes involving approximately 18 000 cases and 58 000 controls[J]. Arch Neurol, 2004, 61: 1652- 1661
[46]Khare A, Ghosh K, Shetty S, et al. Combination of thrombophilia markers in acute myocardial infarction of the young[J]. Indian J Med Sci, 2004, 58:381-388
[47]:Moatti D, Seknadji P, Galand C, et al. Polymorphisms of the tissue factor pathway inhibitor(TFPI)gene in patients with acute coronary syndromes and in healthy subjects: impact of the V264M substitution on plasma levels of TFPI[J]. Arterioscler Thromb Vasc Biol, 1999, 19:862-869
[48]Moatti D, Haidar B, Fumeron F, et al. A new T-287C polymorphism in the 5` regulatory region of the tissue factor pathway inhibitor gene. Association study of the T-287C and C-399T polymorphisms with coronary artery disease and plasma TFPI levels[J]. Thromb Haemost, 2000, 84:244-249
[49]唐雪元,郑兰香,赖少娟,等.脑梗死患者组织因子途径抑制物C-399T多态性[J].中华血液学杂志, 2006, 27:640-642
[50]Naumnik B, Borawski J, Mysliwiec M. Different effects of enoxaparin and unfractionated heparin on extrinsic blood coagulation during haemodialysis: a prospective study[J]. Nephrol Dial Transplant, 2003, 18:1376-1382
[1] Woodward M, Love GD, Rumley A, et al. Fibrinogen as a risk factor for coronary hart disease and mortality in middle-aged men and women. The Scottish heart health study[J]. Enr Heart J, 1998, 19:55-62
[2] Montalescot G, Coller JP, Choussa T, et al. Fibrinogen as a risk factor for coronary heart disease[J]. Eur Heart J, 1998, 19: 1-7
[3] Acevedo M, Foody JM, Pearce GL, et al. Fibrinogen:associations with cardiovascular events in an outpatient clinic [J]. Am HeartJ, 2002, 143 :277-282
[4]王振义,李家增,阮长耿.血栓与止血[M].第三版.上海:上海科学技术出版社, 2004, 534
[5]王现亭,马存建,周玉洁,等.脑梗死人纤维蛋白原性能研究[J].血栓与止血学, 2003, 9:28-29
[6]何蕴,马丽丽,邢秀萍?进展性脑梗死急性期纤维蛋白原和纤溶指标的动态变化及其意义[J].血栓与止血学, 2003, 9:129-130
[7] Martishainen M, Pohjasavvra T, Mikkelsson J et al. Fibrinogen gense promoter-455A allele as a risk factor for lacunar stroke[J]. Stroke, 2003, 342886-891
[8]马会利,葛均治,王颖,等.纤维蛋白原及其相关基因p148和p854多态性与冠心病发病的相关性[J].中国动脉硬化杂志, 2005, 13:351-354
[9] Gomez K, Mcvey JH. Tissue factor initiated blood coagulation[J]. Front-Biosci, 2006, 11:1349-1359
[10]Mackman N, Tilley RE, Key NS. Role of the extrinsic pathway of blood coagulation in hemostasis and thrombasis[J]. Arterioscler Thromb Vasc Biol, 2007, 7:[Epub ahead of print]
[11]Versteeg HH. Tissue factor as an evolutionary conserved cytokine receptor: implications for inflammation and signal transduction [J]. Semin Hemato1, 2004, 41(suppl 1) :168-172
[12]Spronk HMH, Van der Voort D, Cate HT. Blood coagulation and the risk of atherothrombosis: a comptex relationship[J]. Thromb J, 2004, 2:1-10
[13]Maly M, Vojacek J, Hrabos V, et al. Tissue factor, tissue factor pathway inhibitor and cytoadhesive motecules in patients with an acute coronary syndrome[J]. Physiol Res, 2003, 52:719-728
[14]Ott I. Tissue factor in acute coronary syndromes[J]. Semin Vosc Med, 2003, 3:185-192
[15]Gomez K, McVey JH, Tuddenham E. Inhibition of coagul, ation by macromolecular complexes[J]. Haernatof J, 2005, 90:1570-1576
[16]Crawtey J, Lupu F, Westmuckett AD, et al. Expression, tocatization, and activity of tissue factor pathway inhibitor in normat and atherosderotic human vessets[J]. Arterioscler Thromb Vasc Biol, 2000, 20:1362-1373
[17]Osterud B. Bjoklid E. Source of tissue factor[J]. Semin Thromb Hemost, 2006, 32:11-23
[18]Vieira LM, Dusse LM, Fernandes AP, et at. Monocytes and ptasma tissue factor revers in normat individuats and patients with deep venous thrombosis of the tower umbs: potential diagnostic toots?[J] Thrornb Res, 2007, 119:157-165
[19]Pereira J, Alfaro G, Goycoolea M, et al. Circulating platelet-derived microparticles in systemic lupus erythematosus. association with increased thrombin generation and procoagulant state[J]. Thromb Haemost, 2006, 95:94-99
[20]Tilley RE, Pedersen B, Pawlinski R, et at. Atheroscterosis in mice is not affected by a reduction in tissue factor expression[J]. Arterioscier Thromb Vosc Bio, 2006, 26:555-562
[21]WiLcox JN, Noguchi S, Casanova J. Extrahepatic synthesis of factorⅦin human atherosderotic vessels[J]. Arterioscler Thromb Vase Biol, 2003, 23:136-141
[22]Migdalski A, Kotschy M, Jawien A. Tissue factor, tissue factor Pathway inhibitor and vascular endothelial growth factor-A in carotid atherosclerotic plaques[J]. Eur J Vasc Endovasc Surg. 2005, 30:41-47
[23]Guo W, Wang H, Zhao W, et al. Effect of alltrans retinoic acid and arsenic trioxide on tissue factor expression in acute promyetocytic teukemia cells[J]. Chfn Med J (Engi), 2001, 114:30-34
[24]Bogdanov VY, Balasubramanian V, Hathcock J, et al. Alternativety spliced human tissue factor: a circulating, soluble, thrombogenic protein[J]. Nat Med, 2003, 9:458-462
[25]Bogdanov VY, Kirk RI, MiLler C, et aL. Identification and characterization of mudne alternatively spliced tissue factor[J]. J Thromb Haernost, 2006, 4:158-167
[26]Meade TW, Mellows S, Brozovic M, et al. Haemostaic timetion and is chaemie heart disease:principal results of the northwick park heart study[J]. Lancet, 1986, 2:533-537
[27]Girelli D, Russoc, Ferracesip, et al. Polymorphisms in the factorⅦgene and the risk of myocardial infarction in patients with coronary artery disease[J]. N Engl J Mod,2000, 343:774-780
[28]Hrozikiewicz PM, Cascorbil, Ziemers et al. Reduced procedural risk for coronary catheter interventions in carries of the coagulatiou factorⅦ-GIn 353 gene[J]. J Am Cell Cardiol, 2000, 36: 1520-1525
[29]康文英,王鸿利,熊立凡,等.脑梗死病人凝血因子Ⅷ水平及其基因多态性研究[J].诊断学理论与实践, 2002, 1:79-81
[30]杨林花,董春霞,魏文宁,等.凝血因子V和凝血因子Ⅷ活性的变化与冠心病的关系[J].临床血液学杂志, 2004, 17:70-73
[31]Folsom AR, Wu KK, Rosamond WD, et al. Prospective study of hemostaic factors and incidence of ooronary heart disease:the atheresclerosis risk in communities (ARIC) study[J]. Cirulation, 1997, 96:1102-1108
[32]Cooper DN, Krawczak M. Venous thrombosis:from genes to clinical medicine [M]. Guidford: Bios Scientifle Publishers, 1997, 119-136
[33]Wu AH, Tsongalis GJ. Correlation of polymorphisms to coagulation and biochemical risk factors for cardiovascular disease[J]. Am J Cardiol, 2001, 87: 1361-1366
[34]熊立凡,倪培华,吴洁敏,等,中国人动脉血栓性疾病与活化蛋白C裂解FV和FⅧ基因位点突变的相关性研究[J].微循环学杂志, 2004, 14:49-51, 54
[35]Cristina L, Benilde C, Michela C, et al. High plasma levels of factorⅧand risk of recurrence of venous thromboembolism[J]. Br J Haematol, 2004, 124 :504-510
[36]Rosendoal FR. High levels of factorⅧand venous thrombosis[J]. Thromb Haemost, 2000, 83:1-2
[37]Mansrelt EPG, Laffan M, Mevey JH. et al. Analysis of the Fg gene in individuals with high plasma factorⅧ:C levels and associated venous thrombosis[J]. Thromb Haemost, 1998, 80: 561-565
[38]阎平,黄庆忠.急性脑梗塞患者血浆凝血因子Ⅷ相关抗原含量和质量测定意义探讨[J].福建医学杂志, 1998, 20:101-102
[39]Soria JM, Almasy L, Souto JC, et al. A new locus on chromosoue 18 that influences. Normal variation in activated protein C resisanee phenotype and factorⅧactivity[J]. Blood, 2003, 101:163-167
[2] Rapaport SI Rao LVM. The tissue factor pathway: How it has become a“prima ballerina”[J]. Thromb Haemost, 1995, 74.:7-17
[3] Gianluca C, Marco V, Paolo F, et al. Tissue factor and cogulation factorⅦlevels during acute myocardial infarction:Association with genotype and adverse events[J]. Arterioscler Thromb Vasc Biol, 2006, 26:2800-2806
[4]贺蓉,贺石林.凝血-抗凝系统与血栓.见刘泽霖?贺石林?李家增主编,血栓性疾病的诊断与治疗[M].北京:人民卫生出版社, 2006, 100
[5] Versteeg HH, Peppelenbosch MP, Spek CA. The pleiotropic effects of tissue factor. a possible role for factorⅦa-induced intracelluar signaling[J]. Thromb Haemost, 2001, 86:1353-1359
[6] Manda’s S K, Pendurthi U R, Rao L V. Cellular localization and trafficking of tissue factor[J]. Blood, 2006, 107:4746-4753
[7] Shebuski RJ, kilgore KS. Role of inflammatory mediators in thrombogenesis[J]. J Pharmacol Exp Ther, 2002, 300:729-735
[8] Pro RT, Sato Y, Mackman N, et al. Mice deficient in tissue factor demonstrate attenuated intimal hyperplasia in response to vascular injury and decreased smooth muscle cell migration[J]. Thromb Haemost, 2004, 92:451-458
[9] Kann KG, Van’t Veer C, Cawthern K, et al. The role of the tissue factor Pathway in initiation of coagulation[J]. Blood Coagul Fibrinolysis, 1998;9 suppl 1:S3-7
[10]贺石林,熊石龙,贺蓉,等. FⅫa受抑稀释凝血活酶试验反映凝血过程的研究[J].中华血液学杂志, 2000, 21:118-121
[11] Savelieva I, BaiPai A, Camm AJ. Stroke in atrial fibrillation:update on Pathophysiology, new antithrombotic therapies, and evolution of Procedures and devices[J]. Ann Med, 2007, 39:371-391
[12] Fredrick R, Pochet L, Charlier C, et al. Modulators of the coagulation cascade:focus and recent advances in inhibitors of tissue factor, factorⅦa and their complex[J]. Curr-Med-Chem, 2005, 12:397-417
[13] Cirillo P, Cali G, Golino P, et al. Tissue factor binding of activated factorⅦtriggers Smoth muscle cell proliferation via extracellular signal-regulated kinase activation[J]. Circulation, 2004, 109:2911-2916
[14] Rao VM, Pendurthi U. Tissue factor-factorⅦa signaling[J]. Arterioscler ThrombVasc Biol, 2005, 25:47-56
[15] Abe Y, Kondo M, Kubota T, et al. Noninvasive assessment of coronary microvascular dysfuntion using TC-99m tetrofosmin SPECT in patients with acute myocardial infarction[J]. J-Nucl-Cardiol, 2004, 11:562-569
[16] Van-der-Putten RF, te-velthuis HT, de-Zwaan C, et al. State and diagnostic value of plasma tissue factor in early-hospitalised patients with chest pain[J]. Br-J-Haematol, 2005, 131:91-99
[17] Meixia He, Zhi bin wen, Xiao fan He, et al. Observation on tissue factor pathway and some other coagulation parameters during the onset of acute cerebrocardiac thrombotic diseases[J]. Thromb Res, 2002, 107:223-228
[18] Bennermo M, Held C, Ericsson CG, et al. Genotype-specific increase in plasma concentrations of activated coagulation factorⅦin response to experimental inflammation. A link between infection and acute myocardial infarction[J]?Thromb Haemost, 2005, 94:427-431
[19]刘伟,综述.组织因子途径抑制物-1与临床疾病的相关性研究[J].国外医学输血及血液学分册, 2004, 27:216-219.
[20] Murray, J, Adams, Jim Thom, et al. The tissue factor pathway in ischemic stroke[J]. Blood Coagulation and Fibrinolysis, 2006, 17:527-532
[21] Golino P, Ravera A, Ragni M, et al. Involvement of tissue factor pathway inhibitor in the coronary circulation of patients with acute coronary syndromes[J]. Circulation 2003, 108:2864-2869
[22] Adama M J, Thom J, Hankey G J, et al. The tissue factor pathway in ischemic stroke[J]. Blood Coagulation and Fibrinolysis, 2006, 17:527-532
[23] Kopp CW, Steiner S, Priglinger U, et al. Parameters of the tissue factor pathway with coumadin/dipyridamole versus ticlopidine as adjunct antithrombotic-drug regimen in coronary artery stenting[J]. Blood Coagul Fibrinolysis 2003, 14:379-386
[24] Sebestjen M, Keber I, Zegura B, et al. Statin and fibrate treatment of combined hyperlipidemia: the effects on some novel risk factors[J]. Thromb Haemost 2004, 92:1129-1135
[25] Bartok A, Steiner S, Seidinger D, et aL. Atorvastatin reduces thrombin generation after percutaneous coronary intervention independent of soluble tissue factor[J]. Thromb Res, 2005, 115:469-474
[26] Kario K, Duell PB, Matsuo T, et aL. High plasma homocysteine levels in elderly Japanese patients are associated with increased cardiovascular disease riskindependently from markers of coagulation activation and endothelial cell damage[J]. Atherosclerosis, 2001, 157:441 -449
[27] Kang WY, Wang HL, Xiong LF, et al. Polymorphisms of the coagulation factorⅦgene and its plasma levels in relation to acute cerebral infarction differences in allelic frequencies between Chinese Han and European populations[J]. Chin Med J (Engl), 2004, 117:71-74
[28] Hirsh J, O’Donnell M, weitz Jl. New anticoagulants[J]. Blood 2005, 105:453-463
[29] Bilgen D, Sonmez H, Ekmekei H, et al. The relationship of TFPI, Lp(a), and oxidized LDL antibody levels in patients with coronary artery disease[J]. Clin Biochem, 2005, 38:92-96
[30] Westrick RJ, Bodary PF, Xu Z, et al. Deficiency of tissue factor pathway inhibitor promotes atherosclerosis and thrombosis in mice[J]. Circulation, 2001, 103:3044-3046
[31] Kato H. Regulation of functions of vascular wall cells by tissue factor pathway inhibitor[J]. Arterioscler Thromb Vasc Biol, 2002, 22:539-548
[32] Lindmark E, Siegbahn A. Tissue fator regulation and cytokine expression in monocyte-endothelial cell co-culturee:effects of a statin, an ACE-inhibitor and a Low-molecular-weight heparin[J]. Thromb Res, 2002, 108:77-84
[33] Piro O, Broge GJ Jr. Comparison of cell-surface TFPIαandβ[J]. J Thromb Haemost, 2005, 3:2677-2683
[34] Lisowski P, Malyszko J, Lisowska A, et al. Role of the hemostatic system in pathogenesis of atherosclerosis as the main etiology of coronary ischemia[J]. Pol Merkuriusz Lek, 2004, 16:465-467
[35]戴宇翔,张抒扬.组织因子和其途径抑制物在冠状动脉疾病及治疗中的作用[J].中华内科杂志, 2005, 44:866-868
[36] Makin AJ, Blann AD, chung N A, et al. Assessment of endothelial damage in atherosclerotic vascular disease by quantification of circulating endothelial cells. Relationship with von willebrand factor and tissue factor[J]. Eur-Heart-J, 2004, 25:371-376
[37] Eilertsen KE, Osterud B. Tissue factor: (patho) physiology and cellular bilolgy[J]. Blood Coagul Fibrinolysis, 2004, 15:521-538
[38] Bochkov VN, Mechtcherinkova D, Lucerna M, et al. Oxidized phospholipids stimulate tissue factor expression in human endothelial cells via activation of EPF/EGR-1 and Ca++/NFAT[J]. Blood, 2002, 99:199-206
[39] Corti R, Hutter R, Badimon JJ, et al. Evolving concepts in the triad of atherosclerosis, inflammation and thrombosis[J]. J Thromb Thrombolysis, 2004, 17:35-44
[40] Moons AH, Levi M, Peters RJ. Tissue factor and coronary artery disease[J]. Cardiovasc Res, 2002, 53:313-325
[41] Banai S, Gertz SD. Tissue factor as therapeutic target in coronary syndromes[J]. Am J cardiol, 2001, 87:763-765
[42] Ardissino D, Merlini PA, Arlens R, et al. Tissue factor in human coronary atherosclerotic plaques[J]. Clin Chim Acta, 2000, 219:235-240
[43] Maier W, Altwegg LA, Corti R. Inflammatory markers at the site of ruptured plaque in acute myocardia infarction: locally increased interleukin-6 and serum amyloid a but decreased C-reactive protein[J]. Circulation, 2005, 111:1355-1361.
[44] Moreno PR, Palacios IF, Leon MN, et al. Histopathologic comparison of human coronary in-stent and post-balloon angioplasty restenotic tissue[J]. Am J Cardiol, 1999, 84:462-466
[45] Ott I, Andrassy M, Zieglgansberger D, et al. Regulation of monocyte procoaguloant activity in acute myocardial infarction:role of tissue factor and tissue factor pathway inhibitor-1[J]. Blood, 2001, 97:3721-3726
[46] Steffel J, Iseli S, Arnet C, et al. Cocaine unbalances endothelial tissue factor and tissue factor pathway inhibitor expression[J]. J Mol Cell Cardiol, 2006, 40:746-749
[47] Saigo M, Abe S, Ogawa M, et al. Imbalance of plasm inogen activator inhibitor-1/tissue plasm inogen activator and tissue factor/tissue factor pathway inhibitor in young Japanese men with myocardial infarction[J]. Tromb Haemost, 2001, 86:1197-1203
[48] Malarstig A, Tenno T, Johnston N, et al. Genetic variations in the tissue factor gene are associated with clinical outcome in acute coronary syndrome and expression levels in human monocytes[J]. Arterioscler Thromb Vasc Biol, 2005, 25:2667-2672
[49] Dahm A, Van Hylckama Vlieg A, Bendz B, et al. Low levels of tissue factor pathway inhibitor (TFPI) increase the risk of venous thrombosis[J]. Blood, 2003, 101:4387-4392
[50] Mizuno O, Ikeda U, Hojo Y et al. Tissue factor expression in coronary circulation as a prognostic factor for late restenosis after coronary angioplasty[J]. Cardiology, 2001, 95:84-89
[51] Ott I, koch W, Von Beckerath N, et al. Tissue factor promotor polymorpnism-603A/G is associated with myocardial infarction[J]. Atherosclerosis, 2004, 177:189-191
[52]胡豫,徐丹梅,孙春艳.缺血性心脏病患者血浆凝血因子Ⅶ与血脂的关系[J].中华内科杂志, 2005, 44:418-420
[53]刘敏娟,周立红,刘世明,等.血浆凝血因子Ⅶ测定在冠心病中的临床意义[J].临床心血管病杂志, 2000, 16:443-444
[54] Di Castelnuovo A, D’Orazio A, Amore C, et al. The decanucleotide insertion deletion polymorphism in the promoter region of the coagulation factorⅦgene and the risk of familial myocardial infarction[J]. Thromb Res, 2000, 98:9-17
[55]康文英,王鸿利,熊立凡,等.冠心病患者血浆凝血因子Ⅶ水平及其基因多态性研究[J].中华血液学杂志, 2002, 23:457-459
[56] Petrovic D, Zorc M, Keber I, et al. Joint effect of G1691 A factor V pointmutation and factorⅦA rg/Gln(353) gene polym orphism on the risk of premature coronary artery disease[J]. Ann Genet, 2001, 44:33-36
[57]徐耕,金国栋,傅国胜,等.凝血因子V和Ⅶ基因多态性与冠心病的初步研究[J].中华医学遗传学杂志, 2003, 20:39-42
[58]宋善俊,夏凌辉.冠状动脉缺血性心脏病与血栓形成.见:王振义,李家增,阮长耿,主编.血栓与止血基础理论与临床[M].上海:上海科学技术出版社, 2004, 529-543
[59] Jander S, sitzer M, wendt A, et al. Expression of tissue factor in high-grade carotid artery stenosis: association with plaque destabilization[J]. stroke, 2001, 32:850-854
[60] Klein BD, White HS, Callahan KS. Cytokine and intracellular signaling regulation of tissue factor expression in astrocytes[J]. Neurochem Int, 2000, 36:441-449
[61] Duering C, Kosch A, Langer C, et al. TFPI is an independent risk factor for thromboembolism and stroke[J]. Thromb Haemost, 2004, 92:707-712
[62]刘立根,段磊,朱宏钧等,腔隙性和动脉粥样硬化性脑梗死急性期患者血浆组织因子的检测[J].中华血液学杂志, 2002, 23:488-489
[63] Zhang X, Xu Y, Hong M, et al. Plasma thrombomodulin, fibrinogen, and activity of tissue factor as risk factor for acute cerebral infarction[J]. Am J Clin Pathol, 2007, 128:287-292
[64]刘泽霖.血栓病的分类?发病机制及危险因素.见刘泽霖?贺石林?李家增主编.血栓性疾病的诊断与治疗[M].北京:人民卫生出版社, 2006, 15
[65]潘学谊,丁彩屏,商谊.血浆凝血因子活性测定在急性缺血性脑卒中的临床研究[J].血栓与止血学, 2004, 10:119-122
[66] Scarabin PY, Aillaud MF, Amouyel P, et al. Associations of fibrinogen, factorⅦand PAI-1 with baseline findings among 10, 500 male participants in a prospective studyof myocadial infarction-the PRIME study. Prospective epidemiological study of myocardial infarction[J]. Thromb Haemost, 1998, 80:749-756
[67]康文英,王鸿利,熊立凡,等.脑梗死病人血浆凝血因子Ⅶ水平及其基因多态性研究[J].诊断学理论与实践, 2002, 1:79-81
[68] Pinotti M, Toso R, Girelli D, et al. Modulation of factorⅦlevels by intron 7 polymorphisms:population and in vitro studies[J]. Blood, 2000, 95:3423-3428
[69] Albers GW. Antithrombotic therapy for prevention and treatment of ischemic stroke[J]. J Thromb Thrombolysis, 2001, 12:19-22
[70] Sacco RL, Adams R, Albers G, et al. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack:a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke:Cosponsored by the Council on cardiovascular radiology and intervention:the American Acedemy of Neurology affirms the value of this guideline[J]. Stroke, 2006, 37:577-617
[71]他汀类药物预防缺血性卒中/短暂性脑缺血发作专家组.他汀类药物预防缺血性卒中/短暂性脑缺血发作的专家建议[J].中华内科杂志, 2007, 46:81-82
[72] Shebuski RJ, kilgore KS. Role of inflammatory mediators in thrombogenesis[J]. J Pharmacol Exp Ther, 2002, 300:729-735
[73] Egorina E M, Sovershaev M A, Osterud B. In-cell Western assay:a new approach to visualize tissue factor in human monocytes[J]. J-Thromb-Haemost, 2006, 4:614-620
[74] Sase T, wada H, KamiKura Y, et al. Tissue factor messenger RNA levels in leukocytes compared with tissue factor antigens in plasma from patients in hypercoagulable state caused by various diseases[J]. Thromb-Haemost, 2004, 92:132-139
[75] Buchs A E, kornberg A, Zahavi M, et al. Increased expression of tissue factor and receptor for advanced glycation end products in peripheral blood mononuclear cells of patients with type II diabetes mellitus with vascular complications[J]. Exp–Diabesity-Res. 2004, 5:163-169
[76] Meixia He, xiao fan He, Qin zhi Xie, et al. Angiotensin II induces the expression of tissue factor and its mechanism in human monocytes[J]. Thrombosis Research, 2006, 117:579-590
[77] Bai-H, Ma-D, Zhang-Y-G, et al. Molecular design and characterization of recombinant long half-life mutants of human tissue factor pathway inhibitor[J]. Thromb-Haemost, 2005, 93:1055-1060
[78] Lupu-C, Hu-X, Lupu-F. Caveolin-1 enhances tissue factor pathway inhibitor exposure and function on the cell surface[J]. J-Biol-Chem, 2005, 280:22308-22317
[79] Audu-P, Nielsen-V-G, Armstead-V, et al. The impact of tissue factor pathway inhibitor on coagulation kinetics determined by thrombelastography[J]. Anesth-Analg, 2006, 103:841-845
[80] Hedner U, Erhardtsen E. Future possibilities in the regulation of the extrinsic pathway:rFⅦa and TFPI[J]. Ann Med, 2002, 32 Suppl 1:68-72
[81] Gerlach R, Scheuer T, Bohm M, et al. Increased levels of plasma tissue factor pathway inhibitor in patients with glioblastoma and intracerebral metastases[J]. Neurol Res, 2003, 25:335-338
[82] Yin X, Yutanin C, Ikeda Y, et al. Tissue factor pathway inhibitor gene delivery using HVJ-AVE liposmes markedly reduces restenosis on atherosclerotic artheries[J]. Cardiovase Res, 2002, 56:454-463
[83] Nishioka T, Yokota M, Hino M, et al. Tissue factor pathway inhibitor can interact with platelets[J]. J Immunol Methods, 2002, 266:181-184
[84] Shimokawa T, Yamamoto K, Kojima T, et al. Down-regulation of murine tissue factor pathway inhibitor mRNA by endotoxin and tumor necrosis factor-alpha in vitro and in vivo [J]. Thromb Res, 2000 ; 100:211-221
[85] Uszynski M, Zekanowska E, Uszynski W, et al. Tissue factor(TF) and tissue factor pathway inhibitor(TFPI)in amniotic fluid and blood plasma:implications for the mechanism of amniotic fluid embolism [J]. Eur J Obstet Gynecol Reprod Biol, 2001,95:163-166
[86] Zemanova P, Opatrny K, Vit L, et al. Tissue factor, its inhibitor, and the thrombogenicity of two new synthetic membranes [J]. Artificial Organs, 2005, 29:651-657
[87] Creasey A A, Reinhart K. Tissue factor pathway inhibitor activity in sevre sepsis [J]. Crit Care Med, 2001,29:126-129
[88] Lwaleed B. A, Bass PS. Tissue factor pathway inhibitor:structure, biology and involvement in disease[J]. J-Pathol, 2006, 208:327-339
[89] Morange PE, Simon C, Alessi MC, et al. Endothelial cell markers and the risk of coronary heart disease: the prospective epidemiological study of myocardial infarction (PRIME) study[J]. Circulation, 2004, 109:1343-1348
[90] Brodin E, Borvik T, Sandset PM, et al. Infarction (MI)-a population-based case-cortrol study[J]. Thromb-Haemost, 2004, 92:178-184
[91] Sandset PM, In:Jespersen J, Bertina, RM, et al. Laboratory techniques in thrombosis-a manual [J]. Dordrecht: Kluwer Academic Publishers BV, 1999,171-181
[92] Ariens RA, Alberio G, Moia M, et al. Low levels of heparin-releasable tissue factor pathway inhibitor in young patients with thrombosis [J]. Thromb Haemost 1999,81:203-207
[93] Kemona-chetnik I, Bodzenta-Lukaszyk A. Kucharewicz I, et al. Tissue factor and tissue factor pathway inhibitor during specific bronchial challenge in allergic asthma patients[J]. Przegl Lek, 2005, 62:98-101
[94]贺石林,李俊成,秦晓群主编.临床生理学[M],北京,科学出版社2001, 138-147
[95]李家增,王鸿利,韩忠朝主编.血液实验学[M],上海科学技术出版社, 1997, 378-380
[96] Hackeng TM, Sere KM, Tans G, et al. Protein s stimulates inhibition of the tissue factor pathway by tissue factor pathway inhibitor[J]. Proc-Natl-Acad-Sci-U-S-A, 2006, 103:3106-3111
[97] Steppich B, Mattisek C, sobczyk D, et al. Tissue factor pathway inhibitor on circulating microparticles in acute myocardial infarction[J]. Thromb Haemost, 2005, 93:35-39
[98] Kaiser B, Hoppensteadt DA, Fareed J. Tissue factor pathway inhibitor: an update of potential implications in the treatment of cardiovascular disorders[J]. Expert Opin Investig Drugs, 2001,10:1925-1935
[99] Keller TT, Nagle C, Te-Velthuis H, et al. Tissue factor serum Levels and the risk of future coronary artery disease in apparenty healthy men and women:the EPIC-Norfolk prospective population study[J]. J-Thromb-Haemost, 2006, 4:2391-2396
[100]Ardissino D, Merlini PA, Bauer KA, et al. Thrombogenic potential of human coronary atherosclerotic plaques[J]. Blood, 2001, 98:2726-2729
[101]王鸿利.凝血因子筛选试验;王鸿利.凝血因子功能活性检测;汉建忠,等.凝血因子激活标志物检测;邵慧珍.纤溶降解产物检测方法.见李家增,王鸿利,韩中朝主编.血液实验学[M].上海,上海科学技术出版社, 1997, 345-428
[102]王学峰.凝血系统的实验室检查;凝血因子的实验室检查.见王振义,李家增,阮长耿主编.血栓与止血基础理论与临床[M].上海,上海科学技术出版社, 2004, 903-914
[103]文志斌,熊石龙,何晓凡,等.急性脑梗死发作期间组织因子途径改变的观察[J].中国危重病急救医学, 2003, 9:529-531
[104]刘敏娟,周立红,董临江,等.血浆凝血因子Ⅶ测定在缺血性心脑血管病中的临床意义[J].中华血液学杂志, 2000, 3:152-153
[105]窦红菊,胡钧培,邹丽芳,等.急性脑梗死患者血栓前体蛋白凝血酶抗凝血酶复合物和D-二聚体的检测及其临床意义[J].血栓与止血学, 2004, 3:115-116
[106]陈南,华守明,卢辉和,等. D-二聚体与纤维蛋白质在冠心病中的临床意义[J].中国微循环, 2006, 10:143-145
[107]Song KS, Kim HK. Plasma levels of tissue factor antigen in patients with non-insulin-dependent diabetes mellitus[J]. Yonsei Med J, 2004, 45:38-42
[108]陈敏.血脂水平与脑梗死的关系[J].上海医学, 2004, 10:772-773
[109]Kural BV. Orem C. Uydu HA, et al. The effects of lipid-lowering therapy on paraoxonase activities and their relationships with the oxidant-antioxidant system in patients with dyslipidemia[J]. Coron Artery Dis, 2004,15:277-283
[110]祁燕,谢自敬,阿不力克木.乌鲁木齐市维吾尔族成年人代谢综合征流行病学调查[J].中国现代医学杂志, 2004, 19:155-156
[111]曾小云,谢自敬,伊力哈木.乌鲁木齐市维吾尔族成年人超重和肥胖的流行病学调查[J].中国临床康复, 2005, 3:17-19
[112]王薇彬,李云,谢自敬,等.乌鲁木齐维吾尔族居民1002人糖?脂代谢紊乱与胰岛素抵抗的关系[J].中国临床康复, 2004,33:7418-7419
[113]Passi SJ. Manchanda SC. Lakshmi R, et al. Blood lipid and glucose levels of adolescents belonging to upper income group as markers for assessing the risk of CAD/DM[J]. Asia Pac J Clin Nutr, 2004,13(suppl):s104
[114]许建平.病因与发病机制.见:刘泽霖,贺石林,李家增主编.血栓性疾病的诊断与治疗[M].北京:人民卫生出版社, 2000, 18-25
[115]Lacoviello L, Di Castelnuovo A, De Knijff P, et al. Polymorphisms in the coagulation factorⅦgene and risk of myocardial infarction[J]. N Engl J Med, 1998, 338:79-85
[116]Sato Y, Hatakeyama K, Yamashita A, et al. Proportion of fibrin and platelets differs in thrombi on ruptured and eroded coronary atherosclerotic plaques in humans[J]. Heart, 2005, 91:526-530
[117]Seljeflot I, Hurlen M, Arnesen H. Increased levels of soluble tissue factor during long-term treatment with warfarin in patients after an acute myocardial infarction[J]. J Thromb Haemost, 2004, 2:726-730
[118]Xu G, Jin G, Fu G, et al. Polymorphisma in the coagulation factorⅦgene and risk of myocardial infarction in patients undergoing coronary angiography[J]. Chin Med J, 2003, 116:1194-1197
[119]Cai Q, Chen J, Ma H, et al. Association of coagulation factorⅦwith the risk of myocardial infarction in Chinese[J]. Chin Med J, 2000, 113:1059-1063
[120]Roldan V, Marin F, Fernandez, et al. Tissue factor /tissue factor pathway inhibitor system and long-term prognosis after acute myocardial infarction[J]. Int J Cardiol, 2001, 78:115-119
[121]Cote R, Wolfson C, Solymoss S, et al. Hemostatic markers in patients at risk of cerebral ischemia[J]. Stroke, 2000, 31:1856-1862
[122]刘泽霖,贺石林,李家增主编.血栓性疾病的诊断与治疗[M].北京:人民卫生出版社, 2000, 18-25
[123]Reganon E, Vila V, Martinez-sales V, et al. Association between inflammation and hemostatic markers in atherothrombotic stroke[J]. Thromb Res, 2003, 112:217-221
[124]Morrissey JH. Tissue factor: A key molecule in hemostatic and nonhemostatic systems[J]. Int J Hematol, 2004, 79:103-108
[125]Tilley R, Mackman N. Tissue factor in hemostasis and thrombosis[J]. Semin-Thromb-Hemost, 2006, 32:5-10
[126]Falciani M, Gori AM, Fedi S, Chiarugi, et al. Elevated tissue factor and tissue factor pathway inhibitor circulating levels in ischaemic heart disease patients[J]. Thromb Haemost, 1998,79:495-9
[127]Freeburn JC, Wallace JM, Strain JJ, et al. Monocyte tissue factor-like activity in post myocardial infarction patients[J]. Br J Haematol, 1998,102:605-8
[128]许建平,曹燕娜,文志斌,等.急性心脑血管血栓性疾病患者血浆FⅦ∶C?FⅧ:C?凝血酶原及纤维蛋白原的变化[J].血栓与止血学, 2001, 7:53-56
[129]Dicastelnuovo A, D’Orazio A, Amore C, et al. The decanucleotide insertion/deletion polymorphism in the promoter region of the coagulation factorⅦgene and the risk of familial myocardial infarction[J]. Thromb Res, 2000, 98:9-17
[130]Osterud B, Bjorklid E. Sources of tissue factor[J]. Semin-Thromb-Hemost, 2006, 32:11-23
[131]Halim A G, Hamidon B B, Cheong S k, et al. The prognostic value of tissue factor levels in acute ischaemic stroke[J]. Singapore Med J, 2006,47:400-403
[132]Leatham EM, Math PMW, Tooze JA, et al. Increased monocytes tissue factor expression in coronary disease[J]. Br Heart J, 1995, 73:10-13
[133]Letter to the Editors-in-chief. Tissue factor and tissue factor pathway inhibitor levels in coronary artery disease:correlation with the severity of atheromatosis [J]. Thrombosis Research, 2007, 04, 013
[134]Falciani M, Gori AM, Fedi S, et al. Elevated tissue factor and tissue factor pathway inhibitor circulating levels in ischaemic heart disease patients[J]. Thromb Haemost, 1998, 79:495-499
[135]王学锋,王鸿利主编.血栓与止血的检测及应用[M].上海:上海世界图书出版公司, 2002, 417-422
[136]Mayer TE, Hamann GF, Brueclcmann HJ. Treatment of basilar artery embolism with a mechanical extraction device:necessity of flow reversal[J]. Stroke, 2002, 33:2232-2236
[137]Shiozaki T, Nakajima Y, Taneda M, et al. Efficacy of moderate hypothermia in patients with severe head injury and intracranial hypertension refractory to mild hypothermia[J]. J Neurosurg, 2003, 99:47-51
[138]Krupinski J, Turu MM, Font Ma, et al. Blood-borne tissue factor activity perdicts major cerebrovascular events in patients undergoing carotid enderterectomy. Result from a 1-year follow-up study[J]. Cerebrovasc Dis, 2008, 25:32-39
[139]王立军.凝血因子Ⅶ研究进展[J].血栓与止血杂志, 2002. 8:42-43
[140]Kraaijenhagen RA, in`t-Anker PS, Koopman MM, et al. High plasma concentration of factorⅦC is a major risk factor for venous thromboembolism[J]. Thromb Haemost, 2000, 83: 5-9
[141]Aron R, Folson, Nend Aleksic. Prospective study of fibrinolytic factors and incident coronary heart disease[J]. Arterioscler Thromb Vasc Biol, 2001, 21:611-613
[142]Mark Barber. Peter Langhorne, Ann Rumley, et al. Hemostatic function and progressing ischemic stroke D-dimer predicts early clinical progression[J]. Stroke, 2004, 35:1421-1425
[143]Ottani F, Galvani M. Prognostic role of hemostatic markers in acute coronary syndromes patients [J]. Clin Chim Acta, 2001, 311:33-39
[144]Li Feng, Zhang Guibin, zhao Wen zhou. Coagulation and fibrinolytic avtivity in patients with acute cerebral infarction[J]. Chin Med J, 2003, 116:475-477
[145]张小平,胡豫,杨焰,等.脑梗死与血浆D-二聚体/纤维蛋白原比值的关系[J].临床血液学杂志, 2006, 19:216-217
[146]Christersson C, Oldgren J, Bylock A, et al. Early decrease in coagulation activity after myocardial infarction is associated with lower risk of new ischaemicevents:observations from the ESTEEM Trial[J]. Eur Heart J, 2007, 28:692-698
[147]夏大胜,综述.组织因子与冠心病[J].中国心血管杂志, 2003, 8:294-297
[148]Jan steffel MD, Thomas F, Luscher MD, et al. Tissue factor in cardiovascular diseases molecular mechanisms and clinical implications[J]. Circulation, 2006, 113:722-731
[149]Matezky S, Tani S, Kangavari S, et al. Smoking increases tissue factor expression in atherosclerotic plaques: Implications for plaques thrombogenicity[J]. Circulation, 2000, 102:602-604
[150]姜德谦,黄秋霞,王俊,等.高甘油三酯冠心病患者血浆凝血因子ⅦC活性研究[J].临床心血管病杂志, 2003, 19:205-206
[151]Viswambharan H. Ming XF. Zhu S. et al. Reconstituted high-density lipoprotein inhibits thrombin-induced endothelial tissue factor expression through inhibition of RhoA and stimulation of phosphatidylinositol 3-kinase but not Akt/endothelial nitric oxide synthase[J]. Circ Res, 2004, 94:918-925
[152]Sambola A, Osende J, Hathcock J, et al. Role of risk factors in the modulation of tissue factor activity and blood thrombogenicity[J]. Circulation, 2003, 107:973-977.
[153]Lim HS, Blann A D, Lip Gy. Soluble CD40 ligand, soluble P-selectin, interleukin-6, and tissue factor in diabetes mellitus: relationships to cardiovascular disease and risk factor intervention[J]. Circulation, 2004, 109:2524-2528.
[154]E to M, Kozai T, Cosention F, et al. Statin prevents tissue factor expression in human endothelial cells: role of Rho/Rho-kinase and Akt pathways[J]. Circulation, 2002, 105:1756-1759.
[155]Brandes RP, Beer S, Ha T, et al. Withdrawal of cerivastatin induces monocyte chemoattractant protein 1 and tissue factor expression in cultured vascular smooth muscle cells[J]. Arterioscler Thromb Vasc Biol, 2003, 23:1794-1800.
[156]Morel O, Toti F, Hugel B, et al. Cellular microparticles:a disseminated storage pool of bioactive vascular effectors[J]. Curr Opin Hematol, 2004, 11:156-164.
[157]Meisel SR, Xu XP, Edgington TS, et al. Differentiation of adherent human monocytes into macrophages markedly enhances tissue factor protein expression and procoagulant activity [J]. Atherosclerosis, 2002, 161:35-43
[158]Becker BF, Heindl B, Kupatt C, et al. Monocyte-endothelial cell and hemostasis[J]. Z Kardiol, 2000, 89:160-167
[159]Kim HK, Song KS, Park YS, et al. Changes of plasma tissue factor and tissue factor pathway inhibitor antigen levels and induction of tissue factor expression onmonocytes in coronary artery disease[J]. Cardiology 2000, 93:31-36.
[160]王蕊,温丙昭,马依彤.急性心肌梗死患者组织因子途径比值改变及其意义[J].中华内科杂志, 2007, 46:762-763.
[161]黄细莲,陈方平.血细胞源性组织因子的研究现状[J].中华内科杂志, 2007, 46:74-75.
[162]Falk E, Fernandez-Ortiz A. Role of thrombosis in atherosclerosis and its complications[J]. Am J Cardiol, 1995, 75:3B-11B
[163]Moreno PR, Palacios IF, Leon MN, et al. Histopathologic comparison of human coromary in-stent and post-balloon angioplasty restenotic tissue[J]. Am J Cardiol, 1999, 84:462-466
[164]Biro E, Sturk-Maquelin KN, Vogel GM, et al. Human cellderived microparticles promote thrombus formation in vivo in a tissue factor-dependent manner[J]. J Thromb Haemost, 2003, 1:2561-2568
[165]Diamant M, Tushuizen ME, Sturk A, et al. Cellular microparticles:new players in the field of vascular disease[J]? Eur J Clin Invest, 2004, 34:392-401
[166]Mackman N, Tilley RE, Key NS. Role of the extrinsic pathway of blood coagulation in hemostasis and thrombosis[J]. Arterioscler Thromb Vasc Biol, 2007, 27:1687-1693
[167]Qsterud B, Bjorklid E. Sources of tissue factor[J]. Semin Thromb Hemost, 2006, 32:11-23
[168]Egorina EM, Swvershaev MA, Bjorkoy G, et al. Intracellular and surface distribution of monocyte tissue factor application to inersubject variability[J]. Arterioscler Thromb Vasc Biol, 2005, 25:1493-1498.
[169]Aras O, Shet A, Bach RR et, al. Induction of microparticle and cell-associated intrvascular tissue factor in human endotoxemia[J]. Blood, 2004, 193:4545-4553.
[170]马琦琳,杨天伦,孙明,等.胰岛素样生长因子-1对内皮细胞活力及组织因子的影响[J].中华血液学杂志, 2007, 28:605-608
[171]Meixia He, Xiaofan He, Qinzhi xie, et al. Angiotensin II induces the expression of tissue factor and its mechanism in human monocytes[J]. Thrombosis Research, 2005, 4:1-11.
[172]Mueller J, Rox JM, Madlener K. Quantitative tissue factor gene expression analysis in whole blood:development and evaluation of a real-time PCR platform[J]. Clin Chem, 2004, 50:245-247
[173]Ozcan M, Morton CT, Solovey A, et al. Whole blood tissue factor procoagulantactivity remains detectable during severe aplasia following bone marrow and periphera blood stem cell transplantation[J]. Thromb Haemost, 2001, 85:250-255
[174]Santucci RA, Ercich J, Larriola J, et al. Measurement of tissue factor activity in whole blood[J]. Thromb Haemost, 2000, 83:445-454
[175]Marsik C, Quehenberger P, Mackman N, et al. Validation of a novel tissue factor assay in experimental human endotoxemia[J]. Thromb Res, 2003, 111:311-315
[176]Muller I, Klocke A, Alex M, et al. Intravascular tissue factor initiates coagulation via circulating microvesicles and platelets[J]. FASEB J, 2003, 17:476-478
[177]Steffel J, Thomas F. Tissue factor in cardiovascular diseases molecular mechanisms and clinical implications[J]. Circulation, 2006, 113: 722-731.
[1] Versteeg HH, Ruf W. Emerging insights in tissue factor-dependent signaling events[J]. Semin-Thromb-Hemost, 2006, 32:24-32
[2] Golino P, Cirillo P, Ragni M, et al. Expression of exogenous tissue factor pathway inhibitor in vivo suppresses thrombus formation in injured rabbit carotid arteries[J]. J Am Coll Cardiol, 2001, 38:569-576
[3] Lwaleed BA, Bass PS. Tissue factor pathway inhibitor: structure, bilolgy and involvement in disease[J]. J Pathol, 2006, 208: 327~339
[4] Xu-C, Hu-Xu-X, Zeng-Y, et al. Simulation of a mathematical model of the role of the TFPI in the extrinsic Pathway of Coagulation[J]. Comput-Biol-Med, 2005, 35:435-445
[5]宋善俊?夏凌辉.冠状动脉缺血性心脏病与血栓形成.见王振义?李家增,阮长耿等主编.血栓与止血基础理论与临床[M].上海:上海科学技术出版社, 2004, 529-544
[6] Dusse LM, Carvalho MG, Cooper AJ, et al. Tissue factor and tissue factor Pathway inhibitor:a potential role in Pregnancy and obsteric vascular complications[J]. Clin-chim-Acta, 2006, 372:43-46
[7] Mackman N. Alternativaly spliced tissue factor-one cut too many[J]. Thromb Haemost, 2007, 97:5-8
[8]Siegbahn A, Johnell M, Sorensen BB, et al. Regulation of chemotaxis by the cytoplasmic domain of tissue factor[J]. Thromb Haemost, 2005, 93:27-34
[9]Szotwski B, Antoniak S, Rauch U. Alternatively spliced tissue factor:a previously unknown piece in the puzzle of hemostasis[J]. Trends Cardiovasc Med, 2006, 16:177-182
[10]Bogdowov V Y,Balasubramanian V,Hathcock J,et al.Alternatively spliced human tissue factor:a circulating soluble,thrombogenic protein[J].Nature Medicine, 2003,9:458-462
[11]Szotowski B,Antoniak S,Pollen W,et al.Procoagulant soluble tissue factor is released from endothelial cells in response to inflammatory cytokines[J].Circ Res,2005,96:1233-1239
[12]Censarek P, Bobbe A, Grandoch M, et al. Alternatively spliced human tissue factor(asHTF) is not pro-coagulant[J]. Taemost, 2007, 97:11-14
[13]Eilertsen KE, Osterud B, Tissue factor:(patho)physiology and cellular biology[J].Blood Coagul Fibrinolysis, 2004, 15:521~538
[14]:Golino P, Cimmino G. Targenting tissue factor as an antithrombotic strategy[J]. Semin Vasc Med, 2003, 3:205-214
[15]Llorente-cortes V, Otero-Vinas M, Camino-Lopez S, et al. Aggregated low-density lipoprotein uptake induces membrane tissue factor Procoagulant activity and microparticle release in human vascular smooth muscle cells[J]. Circulation, 2004, 110:452-459
[16]Chou J, Mackman N, Merrill-Skoloff G, et al. Hematopoietic cell-derived microparticle tissue factor contributes to fibin formation during thrombus propagation[J]. Blood, 2004, 104:3190-3197
[17]Day SM, Reeve JT, Pedersen B, et al. Macrovascular thrombosis is driven by tissue factor derived primarily from the blood vessel wall[J]. Blood, 2005, 105:192-198
[18]Morrissey TH. Clotting hits the wall[J]. Blood, 2005, 105:3-4
[19]Butenas S, Bouchard BA, Brummel-ziedins KE, et al. Tissue factor activity in whole blood[J]. Blood, 2005, 105:2764-2770
[20]黄细莲,陈方平,杜建伟,等.血栓性疾病血小板相关组织因子水平及活性的改变化及意义[J].中华内科杂志, 2005, 8:216-218
[21] Aagaard S, Hjordal VE, Barker JH. The efficacy of tissue factor pathway inhibitor (TFPI) as topically applied antithrombotic agent[J]. APMIS Suppl, 2003: 102-107
[22]Dahm AE, Andersen TO, Rosendaal F, et al. A novel anticoagulant activity assay of tissue factor pathway inhibitor(TFPI) [J]. J Thromb Haemost, 2005, 3:651-658
[23]Piro O,Broge GJ.Jr.Comparison of cell-surface TFPIαandβ[J].J Thromb Haemost 2005,3:2677-2683
[24]Jayachandran M, Sanzo A, Owen WG, Miller VM. Estrogenic regulation of tissue factor and tissue factor pathway inhibitor in platelets[J]. Am J Physiol Heart Circ Physiol, 2005, 289: H1908 -1916
[25]Becker RC, Alexander JH, Li Y, Robertson T, et al. Vascular endothelial tissue factor pathway inhibitor kinetics in culture following exposure to DX-9065a—a selective and direct factor Xa inhibitor[J]. J Thromb Thrombolysis, 2004, 18:193-197.
[26] Ndonwi M, Broze G Jr, Bajaj SP. The first epidermal growth factor-like domains of factor Xa and factorⅨa are important for the activation of the factorⅦ—tissue factor complex[J]. Thromb Haemost, 2005, 3:112-118
[27]Brodin E, Iversen N, Hansen JB. Impact of native VLDL on tissue factor pathway inhibitor in endotheliai cells and interactions between TFPIand lipoprotein lipase[J]. JLab Clin Med, 2006, 147:167-173
[28]Walker CP, Royston D. Thrombin generation and its inhibition:a review of the scientific basis and mechanism of action of anticoagulant therapies[J]. Br J A Naesth, 2002, 88:848-863
[29]Sierko E, Zauadzki RJ, Wojtukiewicdz MZ. Tissue factor pathway inhibitors[J]. Pol Merkuriusz Lek, 2002, 13:66-69
[30]Jude B, Zawadzki C, Susen S, et al. Relevance of tissue factor in cardiovascular disease[J]. Arch Mal Coeur Vaiss, 2005, 98:667-671
[31]Marutsuka K, Hatakeyama K, Yamashita A, et al. Role of thrombogenic factors in the development of atherosclerosis[J]. J Atheroscler Thromb, 2005, 12:1-8
[32]Cozzi E, Wingard C J, Cascio W E, et al. Effect of ambient particulate matter exposure on hemostasis[J]. Translational Research, 2007, 149:324-332
[33]Moreno PR. Pathophysiology of plaque disruption and thrombosis in acute ischemic syndromes[J]. J Stroke Cerebrovasc Dis, 2001, 10(2 pt 2):2-9
[34]Moons AH, Levi M, Peters R J, Tissue factor and coronary artery disease[J]. Cardiovasc Res, 2002, 53:313-325
[35]Dahm A, Van Hylckama Vlieg A, Bendz B, et al. Low levels of tissue factor pathway inhibitor (TFPI) increase the risk of venous thrombosis[J]. Blood, 2003, 101:4387-4392
[36]Porta B, Baldassarre D, Camera M, et al. E-selectin and TFPI are associated with carotid intima-media thickness in stable IHD patients:The baseline findings of the MIAMI study[J]. Nutr Metab Cardiovasc Dis, 2007, 20;[Epub ahead of print]
[37]Al-Nozha MM, Abdel–Gader AG, Arafah MR, et al. Tissue factor pathway inhibitor, natural coagulation inhibitors and hemostatic activation markers in patients with acute coronary syndromes[J]. Saudi Med J, 2005, 26:937-942
[38]Kopp CW, Holzenbein T, Steiner S, et al. Inhibition of restenosis by tissue factor pathway inhibitor: in vivo and in vitro evidence for suppressed monocyte chemoattraction and reduced gelatinolytic activity[J]. Blood, 2004, 103:1653-1661
[39]Lwaleed BA, Bass PS. Tissue factor pathway inhibitor:structure, biology and involvement in disease[J]. J Phatol, 2006, 208:327-339
[40]Ott I, koch W, Von Beckerath N, et al. Tissue factor promotor polymorpnism-603A/G is associated with myocardial infarction[J]. Atherosclerosis, 2004, 177:189-191
[41]Liu M, Wu B, Wang WZ, et al. Stroke in China: epidemiology, prevention, and management stategids[J]. Lancet Neurol, 2007, 6: 456-464
[42]Charles W, Cathie S, Martin D et al. Stroke[J]. Lancet, 2003, 362: 1211-1224
[43]Wen ZB, Xiong SL, He XF, et al. Observation on tissue factor pathway during the onset of acute cerebral infarction[J]. Zhongguo Wei Zhong Bing JI Jiu Yi Xue, 2003, 15:529-531
[44]Hassan A, Hunt BJ, O`sullivan M, et al. Markers of endothelial dysfunction in lacunar infarction and ischaemic leukoaraiosis [J]. Brain, 2003, 126 (pt2): 424-432
[45]Casas JP, Hingorani AD, Bautista LE, et al. Meta-analysis of genetic studies in ischemic stroke: thirty-two genes involving approximately 18 000 cases and 58 000 controls[J]. Arch Neurol, 2004, 61: 1652- 1661
[46]Khare A, Ghosh K, Shetty S, et al. Combination of thrombophilia markers in acute myocardial infarction of the young[J]. Indian J Med Sci, 2004, 58:381-388
[47]:Moatti D, Seknadji P, Galand C, et al. Polymorphisms of the tissue factor pathway inhibitor(TFPI)gene in patients with acute coronary syndromes and in healthy subjects: impact of the V264M substitution on plasma levels of TFPI[J]. Arterioscler Thromb Vasc Biol, 1999, 19:862-869
[48]Moatti D, Haidar B, Fumeron F, et al. A new T-287C polymorphism in the 5` regulatory region of the tissue factor pathway inhibitor gene. Association study of the T-287C and C-399T polymorphisms with coronary artery disease and plasma TFPI levels[J]. Thromb Haemost, 2000, 84:244-249
[49]唐雪元,郑兰香,赖少娟,等.脑梗死患者组织因子途径抑制物C-399T多态性[J].中华血液学杂志, 2006, 27:640-642
[50]Naumnik B, Borawski J, Mysliwiec M. Different effects of enoxaparin and unfractionated heparin on extrinsic blood coagulation during haemodialysis: a prospective study[J]. Nephrol Dial Transplant, 2003, 18:1376-1382
[1] Woodward M, Love GD, Rumley A, et al. Fibrinogen as a risk factor for coronary hart disease and mortality in middle-aged men and women. The Scottish heart health study[J]. Enr Heart J, 1998, 19:55-62
[2] Montalescot G, Coller JP, Choussa T, et al. Fibrinogen as a risk factor for coronary heart disease[J]. Eur Heart J, 1998, 19: 1-7
[3] Acevedo M, Foody JM, Pearce GL, et al. Fibrinogen:associations with cardiovascular events in an outpatient clinic [J]. Am HeartJ, 2002, 143 :277-282
[4]王振义,李家增,阮长耿.血栓与止血[M].第三版.上海:上海科学技术出版社, 2004, 534
[5]王现亭,马存建,周玉洁,等.脑梗死人纤维蛋白原性能研究[J].血栓与止血学, 2003, 9:28-29
[6]何蕴,马丽丽,邢秀萍?进展性脑梗死急性期纤维蛋白原和纤溶指标的动态变化及其意义[J].血栓与止血学, 2003, 9:129-130
[7] Martishainen M, Pohjasavvra T, Mikkelsson J et al. Fibrinogen gense promoter-455A allele as a risk factor for lacunar stroke[J]. Stroke, 2003, 342886-891
[8]马会利,葛均治,王颖,等.纤维蛋白原及其相关基因p148和p854多态性与冠心病发病的相关性[J].中国动脉硬化杂志, 2005, 13:351-354
[9] Gomez K, Mcvey JH. Tissue factor initiated blood coagulation[J]. Front-Biosci, 2006, 11:1349-1359
[10]Mackman N, Tilley RE, Key NS. Role of the extrinsic pathway of blood coagulation in hemostasis and thrombasis[J]. Arterioscler Thromb Vasc Biol, 2007, 7:[Epub ahead of print]
[11]Versteeg HH. Tissue factor as an evolutionary conserved cytokine receptor: implications for inflammation and signal transduction [J]. Semin Hemato1, 2004, 41(suppl 1) :168-172
[12]Spronk HMH, Van der Voort D, Cate HT. Blood coagulation and the risk of atherothrombosis: a comptex relationship[J]. Thromb J, 2004, 2:1-10
[13]Maly M, Vojacek J, Hrabos V, et al. Tissue factor, tissue factor pathway inhibitor and cytoadhesive motecules in patients with an acute coronary syndrome[J]. Physiol Res, 2003, 52:719-728
[14]Ott I. Tissue factor in acute coronary syndromes[J]. Semin Vosc Med, 2003, 3:185-192
[15]Gomez K, McVey JH, Tuddenham E. Inhibition of coagul, ation by macromolecular complexes[J]. Haernatof J, 2005, 90:1570-1576
[16]Crawtey J, Lupu F, Westmuckett AD, et al. Expression, tocatization, and activity of tissue factor pathway inhibitor in normat and atherosderotic human vessets[J]. Arterioscler Thromb Vasc Biol, 2000, 20:1362-1373
[17]Osterud B. Bjoklid E. Source of tissue factor[J]. Semin Thromb Hemost, 2006, 32:11-23
[18]Vieira LM, Dusse LM, Fernandes AP, et at. Monocytes and ptasma tissue factor revers in normat individuats and patients with deep venous thrombosis of the tower umbs: potential diagnostic toots?[J] Thrornb Res, 2007, 119:157-165
[19]Pereira J, Alfaro G, Goycoolea M, et al. Circulating platelet-derived microparticles in systemic lupus erythematosus. association with increased thrombin generation and procoagulant state[J]. Thromb Haemost, 2006, 95:94-99
[20]Tilley RE, Pedersen B, Pawlinski R, et at. Atheroscterosis in mice is not affected by a reduction in tissue factor expression[J]. Arterioscier Thromb Vosc Bio, 2006, 26:555-562
[21]WiLcox JN, Noguchi S, Casanova J. Extrahepatic synthesis of factorⅦin human atherosderotic vessels[J]. Arterioscler Thromb Vase Biol, 2003, 23:136-141
[22]Migdalski A, Kotschy M, Jawien A. Tissue factor, tissue factor Pathway inhibitor and vascular endothelial growth factor-A in carotid atherosclerotic plaques[J]. Eur J Vasc Endovasc Surg. 2005, 30:41-47
[23]Guo W, Wang H, Zhao W, et al. Effect of alltrans retinoic acid and arsenic trioxide on tissue factor expression in acute promyetocytic teukemia cells[J]. Chfn Med J (Engi), 2001, 114:30-34
[24]Bogdanov VY, Balasubramanian V, Hathcock J, et al. Alternativety spliced human tissue factor: a circulating, soluble, thrombogenic protein[J]. Nat Med, 2003, 9:458-462
[25]Bogdanov VY, Kirk RI, MiLler C, et aL. Identification and characterization of mudne alternatively spliced tissue factor[J]. J Thromb Haernost, 2006, 4:158-167
[26]Meade TW, Mellows S, Brozovic M, et al. Haemostaic timetion and is chaemie heart disease:principal results of the northwick park heart study[J]. Lancet, 1986, 2:533-537
[27]Girelli D, Russoc, Ferracesip, et al. Polymorphisms in the factorⅦgene and the risk of myocardial infarction in patients with coronary artery disease[J]. N Engl J Mod,2000, 343:774-780
[28]Hrozikiewicz PM, Cascorbil, Ziemers et al. Reduced procedural risk for coronary catheter interventions in carries of the coagulatiou factorⅦ-GIn 353 gene[J]. J Am Cell Cardiol, 2000, 36: 1520-1525
[29]康文英,王鸿利,熊立凡,等.脑梗死病人凝血因子Ⅷ水平及其基因多态性研究[J].诊断学理论与实践, 2002, 1:79-81
[30]杨林花,董春霞,魏文宁,等.凝血因子V和凝血因子Ⅷ活性的变化与冠心病的关系[J].临床血液学杂志, 2004, 17:70-73
[31]Folsom AR, Wu KK, Rosamond WD, et al. Prospective study of hemostaic factors and incidence of ooronary heart disease:the atheresclerosis risk in communities (ARIC) study[J]. Cirulation, 1997, 96:1102-1108
[32]Cooper DN, Krawczak M. Venous thrombosis:from genes to clinical medicine [M]. Guidford: Bios Scientifle Publishers, 1997, 119-136
[33]Wu AH, Tsongalis GJ. Correlation of polymorphisms to coagulation and biochemical risk factors for cardiovascular disease[J]. Am J Cardiol, 2001, 87: 1361-1366
[34]熊立凡,倪培华,吴洁敏,等,中国人动脉血栓性疾病与活化蛋白C裂解FV和FⅧ基因位点突变的相关性研究[J].微循环学杂志, 2004, 14:49-51, 54
[35]Cristina L, Benilde C, Michela C, et al. High plasma levels of factorⅧand risk of recurrence of venous thromboembolism[J]. Br J Haematol, 2004, 124 :504-510
[36]Rosendoal FR. High levels of factorⅧand venous thrombosis[J]. Thromb Haemost, 2000, 83:1-2
[37]Mansrelt EPG, Laffan M, Mevey JH. et al. Analysis of the Fg gene in individuals with high plasma factorⅧ:C levels and associated venous thrombosis[J]. Thromb Haemost, 1998, 80: 561-565
[38]阎平,黄庆忠.急性脑梗塞患者血浆凝血因子Ⅷ相关抗原含量和质量测定意义探讨[J].福建医学杂志, 1998, 20:101-102
[39]Soria JM, Almasy L, Souto JC, et al. A new locus on chromosoue 18 that influences. Normal variation in activated protein C resisanee phenotype and factorⅧactivity[J]. Blood, 2003, 101:163-167