血中检测增强凝血因子及抑制纤溶酶原活化关键基因定量诊断DVT相关研究
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摘要
[目的]
1.通过对DVT大鼠静脉组织基因检测,利用Ncbi Gene生物信息平台,锁定早期与凝血因子Ⅴ、Ⅷ、Ⅹ、组织型纤溶酶原激活抑制物变化高度相关的上游基因,并在DVT大鼠和DVT患者血液中确定它们的表达变化。
2.应用Genecard gene、Coagulation Pathway基因通路信息平台,分析上述部分关键基因与内皮细胞损伤及凝血增强之间的联系,发现内皮细胞线粒体膜通透性增加,导致内皮细胞损伤、分泌抗凝蛋白C减少,Ⅴ、Ⅷ、Ⅹ凝血因子生成增多、活性增强；应用Kegg、GEO、Fibrinolytic Pathway、Platelet Activation信号通路,分析上述部分关键基因与血小板聚集及纤溶活性抑制之间的联系,发现血小板膜上桥接血小板聚集的糖蛋白受体活性增强,血小板聚集增加,血小板释放纤溶酶原活化抑制物增多,纤溶酶原减少。
3.通过研究发现TGF-β1等基因表达上调,其意义在于,在创伤性DVT中,以这些基因为线索,结合基因信息分析技术,能够快速锁定影响血栓复杂问题本质的关键角色,进而更有针对性的开展相关方面的机理深入研究工作,进一步清晰的阐明深静脉血栓形成的机制；同时,使寻找到新的、灵敏的可靠深静脉血栓诊断分子标志物变得更有科学依据和支撑。
[材料和方法]
1.构建大鼠DVT模型,将60只SD大鼠随机分为A组(对照组,n=10只)、B组(血栓形成前组,创伤后2.5小时,n=10只)、C组(血栓形成组,创伤后25小时)、D组(血栓不形成组,创伤后25小时)。在相应时间点解剖大鼠股静脉,观测血栓形成情况,获取相应状态的股静脉组织。采用Genechip Rat Genome2302.0基因芯片检测股静脉壁组织中差异表达的基因；进一步采用倍数变化分析法(Fold Change, FC)筛选出显著差异表达的基因；结合研究热点和最新Ncbi Gene和Gene Card数据库(2013年)、Pathway分析,锁定Serpine1等抗纤基因及相关调控基因(TGF-β1等)为研究重点。
2.建立大鼠DVT模型,将60只大鼠随机分为A组(对照组,n=10只)、B组(血栓形成前组,创伤后2.5小时,n=10只)、C组(血栓形成组,创伤后25小时)、D组(血栓不形成组,创伤后25小时)。在相应时间点获取大鼠血液样本,定性及定量PCR检测上一步锁定的TGF-β1等目的基因的表达。
3.通过最新Ncbi Gene和GeneCard数据库(2013年)获得大鼠与人群的TGF-β1、 Serpine1、vWF、PF4注释信息,将两者的基因序列代入BLAST中进行比较,明确其在大鼠与人类之间的同源性。
4.参照《静脉血栓栓塞症预防的NICE指南》和《美国胸科医师协会抗栓与血栓预防临床实践指南-深静脉血栓形成的诊断》,统一本课题临床研究的DVT高危因素和诊断标准。收集2009年1月～2011年1月,在昆明医科大学第一附属医院骨科住院,有血栓高危因素的患者300例,性别、年龄不限,选取其中血栓形成者12例为血栓形成组(B组)、创伤后无血栓形成者15例为创伤组(C组),另外于健康体检人群收集10例为正常对照组(A组)。采集患者的静脉血液,采用PCR和real-time PCR检测TGF-β1、Serpine1、vWF、PF4基因的表达变化,并采用Pathway生物信息学分析,探讨血栓形成过程中TGF-β1、Serpine1、PF4和vWF的表达变化,以及在内皮细胞损伤、血小板聚集、凝血、抗纤中的作用。
[结果]
1.基因芯片检测大鼠DVT股静脉组织：差异表达基因2458个,其中上调1146个；下调1312个；锁定目的基因TGF-β1、Serpine1、vWF和PF4作为进一步研究对象。
2.创伤后2.5小时,大鼠血中TGF-β1、Serpine1、vWF及PF4表达呈现上调。血栓形成后,以上基因表达显著上调,C组(血栓形成组)高于B组(血栓形成前组)及D组(血栓不形成组)(P<0.05)。
3.大鼠与人BLAST对比：TGF-β1为89.4%,Serpine1为91.2%,vWF为86.9%,PF4为92.6%。同源性对比率均高于85%,说明TGF-β1等基因在大鼠与人类之间有较高同源性。
4.临床患者血细胞中PCR检测结果：TGF-β1、Serpine1、vWF、PF4表达水平在B组(血栓形成组)中最高,C组(创伤组)次之,均高于A组(正常对照组)(P<0.05)；进一步的Pathway分析提示：TGF-β1为Serpine1的上游调控基因,Serpine1为vWF的上游调控基因,vWF可调控PF4分泌而活化血小板。
[结论]
1. TGF-β1、Serpine1、vWF、PF4与大鼠、人深静脉血栓形成均有密切联系。
2. TGF-β1、Serpine1、vWF、PF4影响血栓形成的重要角色：血管内皮和血小板,导致凝血增强、抗纤减弱,促进血栓形成。
3. TGF-β1、Serpine1、vWF、PF4在血栓将形成时表达明显升高,血栓形成后逐步升高,促进血栓形成；可以作为预测诊断深静脉血栓形成的分子标志物,其机理需进一步研究并验证其可靠性；同时,使下一步通过细胞系、动物水平DVT分子机制研究更有针对性。再扩大临床样本,验证在血栓形成前的表达变化,最终确定敏感的、可靠的DVT预测诊断的标志物。
1. By testing genes in venous tissue of DVT rats and using Bioinformatics, lock the upstream genes highly relevant with coagulation factor Ⅴ, Ⅷ, Ⅹ and tissue-type plasminogen activator inhibitor. Then test the gene expression changes in blood of DVT rats, patients.
2. Through genetic pathway, analyze the relationship between key genes with the injury of endothelial cell and enhancing of coagulation, discovering that the permeability of mitochondrial membrane in endothelial cells increase, leading to the decreasing of anticoagulant protein C secretion, and increasing of Ⅴ, Ⅷ, Ⅹ coagulation factor activity; analyze the relationship between key genes with platelet aggregation and Inhibition of fibrinolytic activity, discovering that the activity of glycoprotein receptor in platelet membrane increase, leading to the increasing of plasminogen activator inhibitor release and decreasing of plasminogen.
3. The related results show that gene expression of TGF-β1and other genes are up-regulated, indicating that in traumatic DVT, focusing on these genes and combining with genetic information analysis, roles influencing the complicated issues of DVT are quickly locked, and is beneficial to the relevant research works on DVT. Meanwhile, diagnostic molecular markers are finally fixed.
MATERIALS AND METHODS
1. Sixty SD rats model of DVT were established and randomly divided into four groups. Group A (control group, n=10), Group B (pre-thrombosis group,2.5hours after trauma, n=10), Group C (thrombosis group,25hours after trauma, n=10), Group D (no thrombosis group,25hours after trauma, n=10). Dissect femoral vein tissues at different time points, observe the incidence and severity of thrombosis. Acquire femoral vein tissues, test differentially expressed genes by Genechip Rat Genome2302.0; select significantly expressed genes by Fold Change (FC) method; combining with research hotspots and databases of Ncbi Gene, Gene Card, Pathway analysis, lock anti-fibrinolysis genes like Serpine1and regulating genes (TGF-β1etc.) as research emphasis.
2. Sixty SD rats model of DVT were established and randomly divided into four groups. Group A (control group, n=10), Group B (pre-thrombosis group,2.5hours after trauma, n=10), Group C (thrombosis group,25hours after trauma, n=10), Group D (no thrombosis group,25hours after trauma, n=10). Acquire venous blood samples in different time points, test previously locked TGF-β1and other genes expression quantitively and qualitatively.
3. Acquire the annotation informations of TGF-β1, Serpine1, vWF and PF4in rats and human by databases of Ncbi Gene and Gene Card (2013). Compare the sequences of two genes in BLAST, and ascertain their homology in rats and human.
4. Establish the risk factors and diagnostic criteria of DVT in the research based on "The NICE guidelines of prophylaxis for venous thromboembolism", and "Methodology for the development of anti-thrombotic therapy and prevention of thrombosis guidelines". From2009.1～2011.1, in the department of orthopedics of the first affiliated hospital of Kumming medical university, collect300blood samples in human with risk factors of DVT without limitations for gender and age. Select10samples in healthy human as Group A,12samples with thrombosis as Group B,15samples without thrombosis after trauma as Group C. Venous blood samples were collected, detect gene expression changes of TGF-β1, Serpine1, vWF and PF4using PCR and real-time PCR. Explore the gene expression changes and their effects in endothelial cell injury, platelet aggregation, coagulation and anti-fibrinolysis.
RESULTS
1. The results of testing femoral vein tissues in DVT rats by gene chip display that:2458genes differential expressed, of which1146up regulated,1312down regulated. anti-fibrinolysis genes of TGF-β1、Serpine1、vWF and PF4were locked as objects in next research.
2.2.5hours after trauma, TGF-β1, Serpine1, vWF, PF4were up regulated in rats blood. After thrombosis, these gene were up regulated significantly. The gene expression in group C (thrombosis) were higher than group B (pre-thrombosis) and Group D (no thrombosis).
3. The results of BLAST comparison between rats and human show that TGF-β1was89.4%, Serpinel was91.2%, vWF was86.9%and PF4was92.6%. Homology comparison rate was all higher than85%, indicating that TGF-β1and other genes have high homology between rats and human.
4. The real-time PCR results in clinical patients'blood display that the expression level of TGF-β1, Serpine1, vWF and PF4in Group B (thrombosis) were the highest, while the expression level of those in Group C (trauma) were also higher, both groups were higher than Group A (control group). The conclusion of Pathway analysis demonstrating that TGF-β1and Serpinel was upper stream regulating gene of vWF, while vWF was a key gene to regulate the secretion of PF4activating platelet.
CONCLUSION
1. The expressions of TGF-β1, Serpine1, vWF and PF4are possibly have relationship with DVT in rats and human.
2. TGF-β1, Serpine1, vWF and PF4affect the injury of endothelial cell and activation of platelet, which are crucial states of coagulation system and anti-fibrinolysis system, prompting the generation of deep vein thrombosis.
3. The expressions of TGF-β1, Serpine1, vWF and PF4were up regulated before thrombosis, and this trend was more significant after thrombosis, indicating that these genes may probably have effects to prompt thrombosis and was able to be the molecular markers for the diagnosis of DVT.
1.通过对DVT大鼠静脉组织基因检测,利用Ncbi Gene生物信息平台,锁定早期与凝血因子Ⅴ、Ⅷ、Ⅹ、组织型纤溶酶原激活抑制物变化高度相关的上游基因,并在DVT大鼠和DVT患者血液中确定它们的表达变化。
2.应用Genecard gene、Coagulation Pathway基因通路信息平台,分析上述部分关键基因与内皮细胞损伤及凝血增强之间的联系,发现内皮细胞线粒体膜通透性增加,导致内皮细胞损伤、分泌抗凝蛋白C减少,Ⅴ、Ⅷ、Ⅹ凝血因子生成增多、活性增强；应用Kegg、GEO、Fibrinolytic Pathway、Platelet Activation信号通路,分析上述部分关键基因与血小板聚集及纤溶活性抑制之间的联系,发现血小板膜上桥接血小板聚集的糖蛋白受体活性增强,血小板聚集增加,血小板释放纤溶酶原活化抑制物增多,纤溶酶原减少。
3.通过研究发现TGF-β1等基因表达上调,其意义在于,在创伤性DVT中,以这些基因为线索,结合基因信息分析技术,能够快速锁定影响血栓复杂问题本质的关键角色,进而更有针对性的开展相关方面的机理深入研究工作,进一步清晰的阐明深静脉血栓形成的机制；同时,使寻找到新的、灵敏的可靠深静脉血栓诊断分子标志物变得更有科学依据和支撑。
[材料和方法]
1.构建大鼠DVT模型,将60只SD大鼠随机分为A组(对照组,n=10只)、B组(血栓形成前组,创伤后2.5小时,n=10只)、C组(血栓形成组,创伤后25小时)、D组(血栓不形成组,创伤后25小时)。在相应时间点解剖大鼠股静脉,观测血栓形成情况,获取相应状态的股静脉组织。采用Genechip Rat Genome2302.0基因芯片检测股静脉壁组织中差异表达的基因；进一步采用倍数变化分析法(Fold Change, FC)筛选出显著差异表达的基因；结合研究热点和最新Ncbi Gene和Gene Card数据库(2013年)、Pathway分析,锁定Serpine1等抗纤基因及相关调控基因(TGF-β1等)为研究重点。
2.建立大鼠DVT模型,将60只大鼠随机分为A组(对照组,n=10只)、B组(血栓形成前组,创伤后2.5小时,n=10只)、C组(血栓形成组,创伤后25小时)、D组(血栓不形成组,创伤后25小时)。在相应时间点获取大鼠血液样本,定性及定量PCR检测上一步锁定的TGF-β1等目的基因的表达。
3.通过最新Ncbi Gene和GeneCard数据库(2013年)获得大鼠与人群的TGF-β1、 Serpine1、vWF、PF4注释信息,将两者的基因序列代入BLAST中进行比较,明确其在大鼠与人类之间的同源性。
4.参照《静脉血栓栓塞症预防的NICE指南》和《美国胸科医师协会抗栓与血栓预防临床实践指南-深静脉血栓形成的诊断》,统一本课题临床研究的DVT高危因素和诊断标准。收集2009年1月～2011年1月,在昆明医科大学第一附属医院骨科住院,有血栓高危因素的患者300例,性别、年龄不限,选取其中血栓形成者12例为血栓形成组(B组)、创伤后无血栓形成者15例为创伤组(C组),另外于健康体检人群收集10例为正常对照组(A组)。采集患者的静脉血液,采用PCR和real-time PCR检测TGF-β1、Serpine1、vWF、PF4基因的表达变化,并采用Pathway生物信息学分析,探讨血栓形成过程中TGF-β1、Serpine1、PF4和vWF的表达变化,以及在内皮细胞损伤、血小板聚集、凝血、抗纤中的作用。
[结果]
1.基因芯片检测大鼠DVT股静脉组织：差异表达基因2458个,其中上调1146个；下调1312个；锁定目的基因TGF-β1、Serpine1、vWF和PF4作为进一步研究对象。
2.创伤后2.5小时,大鼠血中TGF-β1、Serpine1、vWF及PF4表达呈现上调。血栓形成后,以上基因表达显著上调,C组(血栓形成组)高于B组(血栓形成前组)及D组(血栓不形成组)(P<0.05)。
3.大鼠与人BLAST对比：TGF-β1为89.4%,Serpine1为91.2%,vWF为86.9%,PF4为92.6%。同源性对比率均高于85%,说明TGF-β1等基因在大鼠与人类之间有较高同源性。
4.临床患者血细胞中PCR检测结果：TGF-β1、Serpine1、vWF、PF4表达水平在B组(血栓形成组)中最高,C组(创伤组)次之,均高于A组(正常对照组)(P<0.05)；进一步的Pathway分析提示：TGF-β1为Serpine1的上游调控基因,Serpine1为vWF的上游调控基因,vWF可调控PF4分泌而活化血小板。
[结论]
1. TGF-β1、Serpine1、vWF、PF4与大鼠、人深静脉血栓形成均有密切联系。
2. TGF-β1、Serpine1、vWF、PF4影响血栓形成的重要角色：血管内皮和血小板,导致凝血增强、抗纤减弱,促进血栓形成。
3. TGF-β1、Serpine1、vWF、PF4在血栓将形成时表达明显升高,血栓形成后逐步升高,促进血栓形成；可以作为预测诊断深静脉血栓形成的分子标志物,其机理需进一步研究并验证其可靠性；同时,使下一步通过细胞系、动物水平DVT分子机制研究更有针对性。再扩大临床样本,验证在血栓形成前的表达变化,最终确定敏感的、可靠的DVT预测诊断的标志物。
1. By testing genes in venous tissue of DVT rats and using Bioinformatics, lock the upstream genes highly relevant with coagulation factor Ⅴ, Ⅷ, Ⅹ and tissue-type plasminogen activator inhibitor. Then test the gene expression changes in blood of DVT rats, patients.
2. Through genetic pathway, analyze the relationship between key genes with the injury of endothelial cell and enhancing of coagulation, discovering that the permeability of mitochondrial membrane in endothelial cells increase, leading to the decreasing of anticoagulant protein C secretion, and increasing of Ⅴ, Ⅷ, Ⅹ coagulation factor activity; analyze the relationship between key genes with platelet aggregation and Inhibition of fibrinolytic activity, discovering that the activity of glycoprotein receptor in platelet membrane increase, leading to the increasing of plasminogen activator inhibitor release and decreasing of plasminogen.
3. The related results show that gene expression of TGF-β1and other genes are up-regulated, indicating that in traumatic DVT, focusing on these genes and combining with genetic information analysis, roles influencing the complicated issues of DVT are quickly locked, and is beneficial to the relevant research works on DVT. Meanwhile, diagnostic molecular markers are finally fixed.
MATERIALS AND METHODS
1. Sixty SD rats model of DVT were established and randomly divided into four groups. Group A (control group, n=10), Group B (pre-thrombosis group,2.5hours after trauma, n=10), Group C (thrombosis group,25hours after trauma, n=10), Group D (no thrombosis group,25hours after trauma, n=10). Dissect femoral vein tissues at different time points, observe the incidence and severity of thrombosis. Acquire femoral vein tissues, test differentially expressed genes by Genechip Rat Genome2302.0; select significantly expressed genes by Fold Change (FC) method; combining with research hotspots and databases of Ncbi Gene, Gene Card, Pathway analysis, lock anti-fibrinolysis genes like Serpine1and regulating genes (TGF-β1etc.) as research emphasis.
2. Sixty SD rats model of DVT were established and randomly divided into four groups. Group A (control group, n=10), Group B (pre-thrombosis group,2.5hours after trauma, n=10), Group C (thrombosis group,25hours after trauma, n=10), Group D (no thrombosis group,25hours after trauma, n=10). Acquire venous blood samples in different time points, test previously locked TGF-β1and other genes expression quantitively and qualitatively.
3. Acquire the annotation informations of TGF-β1, Serpine1, vWF and PF4in rats and human by databases of Ncbi Gene and Gene Card (2013). Compare the sequences of two genes in BLAST, and ascertain their homology in rats and human.
4. Establish the risk factors and diagnostic criteria of DVT in the research based on "The NICE guidelines of prophylaxis for venous thromboembolism", and "Methodology for the development of anti-thrombotic therapy and prevention of thrombosis guidelines". From2009.1～2011.1, in the department of orthopedics of the first affiliated hospital of Kumming medical university, collect300blood samples in human with risk factors of DVT without limitations for gender and age. Select10samples in healthy human as Group A,12samples with thrombosis as Group B,15samples without thrombosis after trauma as Group C. Venous blood samples were collected, detect gene expression changes of TGF-β1, Serpine1, vWF and PF4using PCR and real-time PCR. Explore the gene expression changes and their effects in endothelial cell injury, platelet aggregation, coagulation and anti-fibrinolysis.
RESULTS
1. The results of testing femoral vein tissues in DVT rats by gene chip display that:2458genes differential expressed, of which1146up regulated,1312down regulated. anti-fibrinolysis genes of TGF-β1、Serpine1、vWF and PF4were locked as objects in next research.
2.2.5hours after trauma, TGF-β1, Serpine1, vWF, PF4were up regulated in rats blood. After thrombosis, these gene were up regulated significantly. The gene expression in group C (thrombosis) were higher than group B (pre-thrombosis) and Group D (no thrombosis).
3. The results of BLAST comparison between rats and human show that TGF-β1was89.4%, Serpinel was91.2%, vWF was86.9%and PF4was92.6%. Homology comparison rate was all higher than85%, indicating that TGF-β1and other genes have high homology between rats and human.
4. The real-time PCR results in clinical patients'blood display that the expression level of TGF-β1, Serpine1, vWF and PF4in Group B (thrombosis) were the highest, while the expression level of those in Group C (trauma) were also higher, both groups were higher than Group A (control group). The conclusion of Pathway analysis demonstrating that TGF-β1and Serpinel was upper stream regulating gene of vWF, while vWF was a key gene to regulate the secretion of PF4activating platelet.
CONCLUSION
1. The expressions of TGF-β1, Serpine1, vWF and PF4are possibly have relationship with DVT in rats and human.
2. TGF-β1, Serpine1, vWF and PF4affect the injury of endothelial cell and activation of platelet, which are crucial states of coagulation system and anti-fibrinolysis system, prompting the generation of deep vein thrombosis.
3. The expressions of TGF-β1, Serpine1, vWF and PF4were up regulated before thrombosis, and this trend was more significant after thrombosis, indicating that these genes may probably have effects to prompt thrombosis and was able to be the molecular markers for the diagnosis of DVT.
引文
[1]Services UDoHaH. The Surgeon General's Call to Action to Prevent Deep Vein Thrombosis and Pulmonary Embolism 2008.
[2]Piovella F, Wang CJ, Lu H, et al. Deep-vein thrombosis rates after major orthopedic surgery in Asia. An epidemiological study based on postoperative screening with centrally adjudicated bilateral venography[J]. Thromb Haemost,2005; 3(12):2664-70.
[3]邱贵兴,戴尅戎,杨庆铭等.预防骨科大手术后深静脉血栓形成的专家建议--深静脉血栓形成预防座谈会纪要[J].中华骨科杂志.2005；25(10)：636-40.
[4]Cha SI, Lee SY, Kim CH, et al. Venous thromboembolism in Korean patients undergoing major orthopedic surgery:a prospective observational study using computed tomographic(CT) pulmonary angiography and indirect CT venography[J]. Korean Med Sci,2010,25(1):28-34.
[5]Byun SS, Kim JH, Kim YJ,et al. Evaluation of deep vein thrombosis with multidetector row CT after orthopedic arthroplasty:a prospective study for comparison with Doppler sonography[J]. Korean J Radiol,2008,9(1):59-66.
[6]付妍,王大为.血栓栓塞性疾病的急诊治疗和预防[J].中国临床医生,2006,34(8)：51-53.
[7]Lerman A,Zeiher AM. Endothelial function:cardiac events[J]. Circulation,2005,111(3):363-368.
[8]Chieko M, Hiroshi D, et al. Endothelial and Antithrombotic Actions of HDL[J]. Circ.Res,2006,98(4): 1352-1364.
[9]Zhi HY and Xiu FM. Recent Advances in Understanding Endothelial Dysfunction in Atherosclerosis[J]. CM&R,2006.
[10]Becker BF, Heindl B, Kupatt C, et al. Endothelial function and hemostasis[J]. Zeitschrift Fur Kardiologie,2000,89(3):160-167.
[11]Reitsma S, Oude Egbrink MG, Heijnen VV, et al. Endothelial glycocalyx thickness and platelet-vessel wall interactions during atherogenesis[J]. Thromb Haemost,2011,8(5):106.
[12]Zhou X, He P.Temporal and spatial correlation of platelet activating factor-induced increases in endothelial [Ca2+]i, nitric oxide, and gap formation in intact venules[J]. Am J Physiol Heart Circ Physiol,2011,13(1):198-209.
[13]Davignon J, Ganz P. Role of endothelial dysfunction in atherosclerosis[J]. Circulation,2004,109(4): 27-32.
[14]Polycystic ovarian syndrome and the risk of cardiovascular disease and thrombosis. Mak W Dokras A[J]. Semin Thromb Hemost,2009,35(7):613-620.
[15]Cohen AT, Agnelli G, Anderson FA, et al. Venous thromboembolism (VTE) in Europe. The number of VTE events and associated morbidity and mortality [J]. Thromb Haemost,2007,98(4):756-764.
[16]A1 Sayegh F, Almahmeed W, A1 Humood S, et al. Global Risk Profile Verification in Patients with Venous Thromboembolism (GRIP VTE) in 5 Gulf countries[J]. Clin Appl Thromb Hemost,2009, 15(3):289-296.
[17]John A. Heit. The Epidemiology of thromboembolism in the community[J], Arteriosclerosis, Thromb Vasc Biol,2008,28(3):370-372.
[18]Zakai NA, Wright J, Cushman M. Risk factors for venous thrombosis in medical inpatients:validation of a thrombosis risk score[J]. Thromb Haemost,2007; 2(12):2156-2161.
[19]Schellong SM. Complete compression ultrasound for the diagnosis of venous thromboembolism[J]. Curr Opin Pulm Med,2004; 10(5):350-355.
[20]Scarvelis D, Wells PS. Diagnosis and treatment of deep-vein thrombosis[J]. CMAJ,2006; 175(9): 1087-1092.
[21]Hacking NM, Hellewell A, Sadler P. Prevention of deep vein thrombosis and pulmonary embolus[J]. Anaesthesia and intensive care medicine,2006; 7(12):449-452.
[22]Pasternak RC, Criqui MH, Fowkes FG, et al. Atherosclerotic Vascular Disease Conference:Writing Group Ⅰ:epidemiology[J]. Circulation,2006; 109(21):2605-2612.
[23]Michell DL, Andrews KL, Woollard KJ, Chin-Dusting JP. Imaging leukocyte adhesion to the vascular endothelium at high intraluminal pressure[J]. Vis Exp,2011; (54).
[24]L. Batty. The incidence and timing of pulmonary embolism following major trauma[J]. Thrombosis Research,2009,40
[25]A.M. Tofigh, M. Karvandi, et al.Incidence and outcome of pulmonary embolism following popliteal venous repair in trauma cases [J]. British Medical Journal.2010.11.028.
[26]Anil Hingorani, Enrico Ascher, Natalia Markevich, et al.Risk factors for mortality in patients with upper extremity and internal jugular deep venous thrombosis [J].Journal of Vascular Surgery,2005, Vol.41 (3), pp.476-478.
[27]Cuc Mai,Daniel Hunt, et al.Upper-extremity Deep Venous Thrombosis:A Review [J].The American Journal of Medicine,2011 124(5):402-407.
[28]M.M.J. Beckers, H.J.T. Ruven, C.A. Seldenrijk, et al.Risk of thrombosis and infections of central venous catheters and totally implanted access ports in patients treated for cancer [J]. Thrombosis Research,2009,125 (4):318-321.
[29]Dominique Farge, Cecile Durant, Stephane Villiers, et al.Lessons from French national guidelines on the treatment of venous thrombosis and central venous catheter thrombosis in cancer patients [J]. Thrombosis Research,2010, Vol.125, pp.S108-S116.
[30]Popovic M, Smiljanic K, Dobutovic B,et al. Thrombin and vascular inflammation[J]. Mol Cell Biochem,2011.
[31]Chan, Wee-Shian, Spencer, Frederick A, Ginsberg, Jeffrey S, et al.Anatomic distribution of deep vein thrombosis in pregnancy [J]. Canadian Medical Association. Journal,2010, Vol.182 (7).
[32]Chan AK, Paredes N, et al.The coagulation system in humans[J]. Methods Mol Biol.2013;992:3-12.
[33]翟振国,王辰.肺栓塞-深静脉血栓形成的研究现状与展望.中国实用内科杂志,2006,10(14)：806-811
[34]Anil Hingorani, Enrico Ascher, Natalia Markevich, et al.Risk factors for mortality in patients with upper extremity and internal jugular deep venous thrombosis [J]. Journal of Vascular Surgery,2005, Vol.41 (3), pp.476-478
[35]Mark A. Jones, Dae Y. Lee, Jocelyn A. Segall, Gregory J. Landry, et al. Characterizing resolution of catheter-associated upper extremity deep venous thrombosis [J]. Journal of Vascular Surgery,2010, Vol.51 (1),pp.108-113.
[36]Engin Deniz Arslan, Suveyda Aksakalli Yesilaras, et al. Prediction of Pretest Probability Scoring Systems in Pulmonary Embolism:Wells, Kline and Geneva [J]. International Journal of Clinical Medicine,2013, Vol.03 (07), pp.731-735.
[37]B.M Wroblewski, Paul D Siney, Patricia A Fleming, et al. Fatal pulmonary embolism and mortality after revision of failed total hip arthroplasties [J]. The Journal of Arthroplasty,2000, Vol.15 (4), pp.437-439.
[38]Dellas C, Puls M, Lankeit M, et al. Elevated heart-type fatty acid-binding protein levels on admission predict an adverse outcome in normotensive patients with acute pulmonary embolism[J]. J Am Coll Cardiol 2010;55(19):2150-2157.
[39]Lankeit M, Kempf T, Dellas C, et al. Growth differentiation factor-15 for prognostic assessment of patients with acute pulmonary embolism[J]. Am J Respir Crit Care Med,2008,177(9):1018-1025
[40]Lankeit M, Konstantinides S.Thrombolysis for hemodynamically stable patients with pulmonary embolism:still searching for the intermediate-risk group[J]. Thromb Res,2009,124(6):647-648.
[41]Susan R. Kahn MD, MSc.The Post-thrombotic Syndrome:The Forgotten Morbidity of Deep Venous Thrombosis[J].Journal of Thrombosis and Thrombolysis,2006,21(1):41-48.
[42]Grewal, Nina K; Martinez, Jorge Trabal; et al.Quantity of clot lysed after catheter-directed thrombolysis for iliofemoral deep venous thrombosis correlates with postthrombotic morbidity[J].Journal of Vascular Surgery,2010,51, (5):1209-1214.
[43]Borjas L, Zabala W, et al. Intragenic polymorphisms of factor Ⅷ and Ⅸ genes and their utility in the indirect diagnosis of carriers of Haemophilias A and B[J]. Invest Clin.2010 Sep;51(3):391-401.
[44]Rachel T.Bond, Jacqueline M. Cohen, Anthony Comerota, et al. Surgical Treatment of Moderate-to-Severe Post-Thrombotic Syndrome[J]. Annals of Vascular Surgery, 2013,27(2):242-258.
[45]Giancarlo Agnelli, Cecilia Becattini. Acute Pulmonary Embolism[J].N Engl J Med 2010,363(4):266-274
[46]Mareike Lankeit,Stavros Konstantinides. Mortality Risk Assessment and the Role of Thrombolysis in Pulmonary Embolism[J].Clinics in Chest Medicine,2010,31(4):303-305.
[47]Mayor A, Hafiz A, Bassat Q, et al. Association of severe malaria outcomes with platelet-mediated clumping and adhesion to a novel host receptor[J]. PLoS One.2011,296(4):194-198.
[48]J.LATELLA, S.DESMARAIS, M.-J.MIRON,et al.Relation between D-dimer level, venous valvular reflux and the development of post-thrombotic syndrome after deep vein thrombosis[J]. Journal of Thrombosis and Haemostasis,2010,8(10):2169-2175.
[49]Kwiatkowski JN, Melchior A. Effects of fibroblast extracellular matrix calcification on platelet adhesion in vitro[J]. Platelets.2008 Sep;19(6):467-470.
[50]Ciltay EJ, Elber JMH, Fibrt CL, et al. Visceral fat accumulation is an important determinate of PAI-1 levels in young, nonbese men and woman modulation by cross-sex hormone administration[J]. Thromb Vase Biol,1998; 18(11):1716-1722.
[51]Eastwood KA, Vaughan A, McCune KH. Mesenteric vein thrombosis associated with anti-thrombin Ⅲ deficiency[J]. Ulster Med J.2009;78(1):53-55.
[52]Mayor A, Hafiz A, Bassat Q, et al. Association of severe malaria outcomes with platelet-mediated clumping and adhesion to a novel host receptor. PLoS One.2011;6(4):19422.
[53]Kwiatkowski JN, Melchior A. Effects of fibroblast extracellular matrix calcification on platelet adhesion in vitro. Platelets.2008;19(6):467-70.
[54]Spiroski I, Kedev S, Antov S,et al. Investigation of SERPINE1 genetic polymorphism in Macedonian patients with occlusive artery disease and deep vein thrombosis[J]. Kardiol Pol,2009; 67(10):1088-94.
[55]Lassila M, Fukami K, Jandeleit-Dahm K, et al. Plasminogen activator inhibitor-1 production is--pathogenetic in experimental murine diabetic renal disease[J]. Diabetologia,2007; 50(6):1315-1326.
[56]Kaplan JC, Kahn A & Chelly. Innegitimate transcription:tis use in the study of inherited desease[J]. Human Mutation,1992,1(3):357-360.
[57]Paul A Kyrle, Sabine Eichinger, Deep vein thrombosis[J]. The Lancet,2005,365(9465):1163-1174.
[58]Skliankina NN, Boldyreva NV, Shcheglovitova ON. Differences in functional activity of cultivated human vascular endothelium received from different donors[J]. Tsitologiia,2011,53(4):341-346.
[59]L6wenberg EC, Meijers JC, Levi M. Platelet-vessel wall interaction in health and disease[J]. Neth J Med,2010,68(6):242-251.
[60]Sandoo A, van Zanten JJ, et al. The endothelium and its role in regulating vascular tone[J]. Open Cardiovasc Med J,2010,23(4):302-312.
[61]His W. Die Haute und Hohlen des Korpers. Basel:Schwighauser,1865.
[62]Ross R, Glomset, JA (1973). Atherosclerosis and the arterial smooth muscle cell:proliferation of smooth muscle is a key event in the genesis of the lesions of atherosclerosis[J]. Science,180 (4093): 1332-1339.
[63]Furchgott RF, Zawadzki JV. the obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine[J].1980,288(5789):373-376.
[64]Maritza J, Prigent-Tessier A, Bagnost T, et al. Time course of vascular arginase expression and activity in spontaneously hypertensive rats[J]. Life Sci,2008,132(80):1128-1134.
[65]Santhanam L, Lim HK, Lim HK, et al. Inducible NO synthase dependent S-nitrosylation and activation of arginase1 contribute to age-related endothelial dysfunction[J]. Circ Res,2008,4(101): 692-702.
[66]Chandani Lewis, Sorenson JP, Richardson DM, et al. Mechanisms of aging-induced impairment of endothelium-dependent relaxation:role of tetrahydrobiopterin[J]. Am J Physiol Heart Circ Physiol, 2004,287(3):2448-2453.
[67]Nishimura H, Tsuji H, Masuda H. Angiotensin Ⅱ increases plasminogen activator inhibitor-1 and tissue factor mRNA expression without changing that of tissue type plasminogen activator or tissue factor pathway inhibitor in cultured rat aortic endothelial cells[J]. Throm Haemost,1997,77(6):1189-1195.
[68]Bizzozer, et al.function of platelet. Blood Coagul Fibrinolysis.1881.
[69]Hoffman M, Monroe DM, Roberts HR. Activated factor Ⅶ activates factors Ⅸ and Ⅹ on the surface of activated platelets:thoughts on the mechanism of action of high-dose activated factor ⅦVII[J].. Blood Coagul Fibrinolysis.1998,9 (suppl 1):S61-S65.
[70]Gnatenko DV, Saenko EL, Jesty J, et al. Human factor Ⅷ can be packaged and functionally expressed in an adenoassociated virus background:applicability to haemophilia A gene therapy [J]. Br J Haematol,1999,104(3):27-36.
[71]Cole VJ, Staton JM, Eikelboom JW, et al. Collagen platelet receptor polymorphisms integrin alpha-betal C807T and GPVI Q317L and risk of ischemic stroke[J].. J Thromb Haemost.2003,27(1): 963-970.
[72]Jackson SP, Nesbitt WS, Kulkarni S. Signaling events underlying thrombus formation[J]. J Thromb Haemost.2003,28(1):1602-1612.
[73]Kuijpers, M. J. E, Schulte, V, Bergmeier, W, et al. Complementary roles of glycoprotein VI and alpha-betal integrin in collagen-induced thrombus formation in flowing whole blood ex vivo[J]. FASEB J,17(3):685-687.
[74]Peter C, et al. Recent Advances in Understanding platelet Dysfunction in thrombosis [J]. Blood,2003, 32(4):314-351.
[75]Hidenori K, et al. Mechanisms of the platelet incoronary artery disease [J]. Arterioscler Thromb Vase Biol,2013,28(1):1672-1677.
[76]Goto S, Tamura N, Ishida H. Ability of anti-glycoprotein Ⅱb/Ⅲa agents to dissolve platelet thrombi formed on a collagen surface under blood flow conditions[J]. J Am Coll Cardiol,2004,44(3): 316-323.
[77]Bigalke B, Stellos K, Geisler T, et al. High plasma levels o adipocytokines are associated with platelet activation in patients with coronary artery disease[J]. Platelets.2010,21(1):11-19.
[78]GC Parry, N Mackman. A set of inducible genes expressed by activated human monocytic and endothelial cells contain kappa B-like sites that specifically bind c-Rel-p65 heterodimers. Journal of Biological Chemistry[J],1994,37(6):12-17.
[79]Harry Holzmuller, Thoma Moll, Renate Hofer-Warbinek, et al. A Transcriptional Repressor of the Tissue Factor Gene in Endothelial Cells[J]. Arteriosclerosis, Thrombosis, and Vascular Biology,1999, 19(3):1804-1811.
[80]Sumanta Mukherjee, Sanjay K Banerjee, Mohua Maulik, et al. Protection against acute adriamycin-induced cardiotoxicity by garlic:Role of endogenous antioxidants and inhibition of TNF-a expression[J]. BMC Pharmacology,2003,15(3):16-21.
[81]Zhi HY, Xiu FM. Recent Advances in Understanding Endothelial Dysfunction in Atherosclerosis[J]. CM&R,2006,17(4):189-194.
[82]Jude B, Zawadzki C, Susen S, et al. Relevance of tissue factor in cardiovascular disease[J].2005, 98(6):667-671.
[83]Eduardo Ramacciottia, Angela E.Hawleya, Shirley K, et al. Proteomics of microparticles after deep venous thrombosis[J]. Thrombosis Research,2010,125(6):123-138.
[84]Nilius B, Droogmans G. Ion channels and their functional role in vascular endothelium[J]. Physiol Rev, 2001; 81 (4):1415-59.
[85]Venturini CM, Weston LK, Kaplan JE. Platelet cGMP, but not cAMP, inhibits thrombin-induced platelet adhesion to pulmonary vascular endothelium[J]. Am J Physiol,1992,263(3):606-612.
[86]Popovic M, Smiljanic K, Dobutovic B, et al. Thrombin and vascular inflammation[J]. Mol Cell Biochem,2011,47(3):81-90.
[87]Hollenberg MD, Laniyonu AA, Saifeddine M, et al. Role of the amino- and carboxyl-terminal domains of thrombin receptor-derived polypeptides in biological activity in vascular endothelium and gastric smooth muscle:evidence for receptor subtypes[J]. Mol Pharmacol,1993,43(6):921-930.
[88]Hiroaki N, Hisanori H, et al. Small GTPase Rho Regulates Thrombin-Induced Platelet Aggregation[J]. Biochemical and Biophysical Research Communications,2001,280(5):970-975.
[89]Schneppenheim R, Budde U. von Willebrand factor:the complex molecular genetics of a multidomain and multifunctional protein[J]. Thromb Haemost,2011,37(1):209-215.
[90]Tsantes AE, Nikolopoulos GK, Tsirigotis P, et al. Direct evidence for normalization of platelet function resulting from platelet count reduction in essential thrombocythemia[J]. Blood Coagul Fibrinolysis,2011,22(6):457-462.
[91]Armin J. Reininger. VWF attributes impact on thrombus formation[J]. Thrombosis research,2008, 122(4):S9-S13.
[92]Van Stralen KJ, et al. Mechanisms of the Factor V Leiden Paradox[J]. Arterioscler Thromb Vasc Biol, 2008,28(2):1872-1877.
[93]Brouwer JL, Bijl M, Veeger, NJ, et al. The contribution of inherited and acquired thrombophilic defects, alone or combined with antiphospholipid antibodies, to venous and arterial thromboembolism in patients with systemic lupus erythematosus[J]. Blood,2004,104(7):143-148.
[94]周欢琴,谢海宝,肖震等,检测血浆uPA、uPAR、t-PA和PAI-1水平在缺血性心脑血管疾病发病中的意义[J],浙江检验医学,2007,4(7)：32-39.
[95]郑美琴,林燕,李宝清等,脑梗死患者血浆vWF、PLG、D-D含量变化与临床意义[J].现代实用医学,2006,9(6)：45-49.
[96]程彦,胡厚源.血小板膜糖蛋白GP Ⅰbα拮抗剂的研究进展[J].心血管病学进展,2013；5(1)：67-69.
[97]阳艾珍,王璐,周俊松.Tyro 3受体酪氨酸激酶调控糖蛋白Ⅵ介导的血小板活化,血栓与止血学,2012；3(02)：354-358.
[98]K L Moore, K D Patel, R E Bruehl, F Li, et al. P-selectin glycoprotein ligand-1 mediates rolling of human neutrophils on P-selectin[J]. Moore et al.128 (4):661.
[99]Robert C. Fuhlbrigge2, J. David Kieffer2, et al. Cutaneous lymphocyte antigen is a specialized form of PSGL-1 expressed on skin-homing T cells[J]. Nature,1997;17(2):978-981.
[100]庄旭琴,霍建丽,杨天雨,等.血小板ADP受体及其拮抗剂的研究进展[J].药物生物技术,2010；32(16)：368-371.
[101]Biochemistry Department, J. H. Holland Laboratory, American Red Cross, et al. The serpin PAI-1 inhibits cell migration by blocking integrin αvβ3 binding to vitronectin[J].Nature 383,441-443.
[102]Feng,Gullans SR.Connecting the dots using gene-expression profiles. The New England journal of medicine 2006;355 (19):2042-2042.
[103]Haley, Dohner K, Bair E, Use of gene-expression profiling to identify prognostic subclasses in adult acute myeloid leukemia. The New England journal of medicine 2004 Apr; 350 (16):1605-16.
[104]Chen X Molecular cloning,characterization and expression of cDNA encoding translatonally controlled tumor protein (TCTP) from Jatropha curcas L.Mol Biol Rep.2011 V38N5:3107
[105]Yajima, Hertel PM, Estes MK, Vaccine-acquired rotavirus in infants with severe combined immunodeficiency. The New England journal of medicine 2010 Jan; 362 (4):314-9.
[106]Takeya M, Yamasaki F, Uzuhashi S, NIASGBdb:NIAS Genebank databases for genetic resources and plant disease information. Nucleic acids research 2011 Jan; 39
[107]Yang YS, Song HD, The gene expression profiling of sporadic pheochromocytoma and novel full-length cDNAs cloning. Endocrine-related cancer 2003 Dec; 10 (4):621-7
[108]Van Hintum TJ, Van Treuren R. Molecular markers:tools to improve genebank efficiency. Cellular & molecular biology letters 2002; 7 (2B):737-44.
[109]Chen CL, Liu IH, Fliesler SJ, et al. Cholesterol suppresses cellular TGF-beta responsiveness: implications in atherogenesis[J]. Cell Sci,2007; 120:3509-3521.
[110]Gonzales JU, Thistlethwaite JR, Thompson BC, et al. Exercise-induced shear stress is associated with changes in plasma von Willebrand factor in older humans. Eur J Appl Physiol,2009; 106(5) 779-784.
[111]Jiang M, Zhao Y, Shen F, et al. Epitope mapping of human VWF A3 recognized by monoclonal antibody SZ-123 and SZ-125 using MALDI mass spectrometry[J]. Int J Hematol.2011;94(3):241-7.
[112]Law RH, Zhang QW, McGowan S, et al. An overview of the Serpin superfamily[J]. Genome Biol, 2006; 7(5):216-220.
[113]Izuhara K, Ohta S, Kanaji S, et al. Recent progress in understanding the diversity of the human ov-Serpin/cladeB Serpin family[J]. Cellular and molecular life sciences,2008,65(16):2541-2553.
[114]Lhermusier T, Van Rottem J, Garcia C, et al. The Syk-Kinase Inhibitor R406 Impairs Platelet Activation and Monocyte Tissue Factor Expression Triggered by Heparin-PF4 Complex Directed Antibodies[J]. Thromb Haemost,2011,65(16):341-353.
[115]Rohan Samarakoonl, Subhanir S. Redox-Induced Src Kinase and Caveolin-1 Signaling in TGF-b1-Initiated SMAD2/3 Activation and PAI-1 Expression[J]. PLoS ONE,6(7):273-284.
[116]Vladimir Leksa, Samuel Godar, et al. TGF-1-induced apoptosis in endothelial cells mediated by M6P/IGFII-R and mini-plasminogen[J]. Journal of Cell Science,118(7):4577-4586.
[117]Rohan Samarakoon, Stephen P. Higgins, et al. TGF-bl-induced plasminogen activator inhibitor-1 expression in vascular smooth muscle cells requires pp60c-src/EGFRY845 and Rho/ROCK signaling[J]. J Mol Cell Cardiol,2008,44(3):527-538.
[118]Marie-Jose Goumansl, Zhen Liu, Peter ten Dijkel, et al.TGF-b signaling in vascular biology and dysfunction[J]. Cell Research,2009,19(3):116-127.
[119]Rohan Samarakoon and Paul J. Higgins, et al.Integration of non-SMAD and SMAD signaling in TGF-β1-induced plasminogen activator inhibitor type-1 gene expression in vascular smooth muscle cells[J]. Thromb Haemost,2008,100(6):976-983.
[120]Hough C, Cameron CL, Notley CR, et al. Influence of a GT repeat element on shear stress responsiveness of the VWF gene promoter[J]. Thromb Haemost,2008,6 (7):1183-1192.
[121]Izuhara K, Ohta S, Kanaji S, et al. Recent progress in understanding the diversity of the human ov-Serpin/cladeB Serpin family[J]. Cellular and molecular life sciences,2008,65(16):2541-2553.
[1]Mangan MS, Kaiserman D, Bird PI. The role of Serpin in vertebrate immunity[J]. Tissue Antigens, 2008;72(1):1-10.
[2]张雷,唐瞻贵,仝向娟.丝氨酸蛋白酶抑制剂和血管内皮生长因子基因在口腔鳞癌中的表达[J].2004；39(5)：420.
[3]曾蕾,曹江,张行.丝氨酸蛋白酶SNC19及其抑制因子在胃癌中的表达[J].中华消化杂志,2004；24(7)：429-430.
[4]Irving JA, Pike RN, Lesk AM, et al. Phylogeny of the Serpin superfamily:implications of patterns of amino acid conservation for structure and function[J]. Genome Res,2000; 10:1845-1864.
[5]Law RH, Zhang QW, McGowan S, et al. An overview of the Serpin superfamily[J]. Genome Biol, 2006; 7(5):216-220.
[6]戚正武.丝氨酸蛋白酶抑制剂的结构与功能[J].生物化学与生物物理进展,1998；15(5)：322-329.
[7]Krowarsch D, Cierpicki T, Jelen F, et al. Canonical protein inhibitors of serine proteases[J]. Cell Mol Life Sci,2003; 60(11):2427-2444.
[8]Gary AS, Phillip IB, Robin WC, et al. The Serpin are an expanding superfamily of structurally similar but functionally diverse proteins[J]. Biological Chmistry,2001; 276(36):33293-33296.
[9]Molnar K, Holderith BN, Csikos G, et al. Distribution of Serpin in the tissues of the tobacco hornworm(Manduca sexta)larvae:Existence of new Serpin possibly encoded by a gene distinct from the Serpin-1 gene[J]. Insect Physiol,2001,47(7):675-687.
[10]Izuhara K, Ohta S, Kanaji S, et al. Recent progress in understanding the diversity of the human ov-Serpin/cladeB Serpin family[J]. Cellular and molecular life sciences,2008,65(16):2541-2553.
[11]Diana VG, Paul S, Kevin M, et al. Serpin:structure, function and molecular evolution[J]. Biochemistry & Cell Biology,2003; 35:1536-1547.
[12]Li W, Johnson DJ, Esmon CT, Huntington JA. Structure of the antithrombin-thrombin-heparin ternary complex reveals the antithrombotic mechanism of heparin[J]. Nat Struct Mol Biol,2004; 11:857-862.
[13]Kounnas MZ, Church FC, Argraves WS, et al. Cellular internalization and degradation of antithrombin Ⅲ-thrombin, heparin cofactor Ⅱ-thrombin, and alpha 1-antitrypsintrypsin complexes is mediated by the low density lipoprotein receptor-related protein[J]. Biol Chem,1996; 271:6523-6529.
[14]张曙光.中国林蛙皮肤丝氨酸蛋白酶抑制剂RCSP12的基因克隆和原核表达[J].水生生物学报,2010；34(03).
[15]Izuhara K, Ohta S, Kanaji S, et al. Recent progress in understanding the diversity of the human ov-Serpin/cladeB Serpin family[J]. Cellular and molecular life sciences,2008; 65(16):2541-2553.
[16]汪世华,王文勇,黄益洲.丝氨酸蛋白酶研究进展[J].福建农业学报,2007；22(4)：453-456.
[17]Mangan MS, Kaiserman D, Bird PI. The role of Serpin in vertebrate immunity[J]. Tissue Antigens, 2008;72(1):1-10.
[18]Pemberton PA, Stein PE, Pepys MB, et al. Hormone binding globulins undergo Serpin conformational change in inflammation[J]. Nature,1988; 336:257-258.
[19]Zou Z, Anisowicz A, Hendrix MJ, et al. A Serpin with tumor-suppressing activity in human mammary epithelial cells[J]. Science,1994; 263:526-529.
[20]Nagata K. Hsp47:a collagen-specific molecular chaperone[J]. Trends Biochem Sci,1996; 21:22-26.
[21]Lomas DA, Evans DL, Finch JT, et al. The mechanism of Zalpha 1-antitrypsin accumulation in the liver[J]. Nature,1992; 357:605-607.
[22]Bruce D, Perry DJ, Borg JY, et al. Thromboembolic disease due to thermolabile conformational changes of antithrombin Rouen-VI(187 Asn→Asp)[J].Clin Invest,1994; 94:2265-2274.
[23]Aulak KS, Pemberton PA, Rosen FS, et al. Dysfunctional C1-inhibitor(At), isolated from a type Ⅱ hereditary-angio-oedema plasma, contains a P1 'reactive centre'(Arg444→His) mutation[J]. J Biochem,1988; 253:615-618.
[24]Davis RL, Shrimpton AE, Holohan PD, et al. Familial dementia caused by polymerization of mutant neuroSerpin[J]. Nature,1999; 401:376-379.
[25]Stein PE, Carrell RW. What do dysfunctional Serpin tell us about molecular mobility and disease?[J]. Nat Struct Biol,1995; 2:96-113.
[26]Mehta J.L, D.Y.Li. Identification and autoregulation of receptor for ox-LDL in cultured human coronary artery endothelial cells[J]. Brioche Biophysical Res Comm,1998; 248:511-514.
[27]Mourik V, Lawrence DA, Loskutoff DJ. Purification of an inhibitor of plasminogen activator(antiactivator)synthesized by endothelial cells[J]. Biol Chem,1984; 259(23):14914-14921.
[28]Ciltay EJ, Elber JMH, Fibrt CL, et al. Visceral fat accumulation is an important determinate of PAI-1 levels in young, nonbese men and woman modulation by cross-sex hormone administration[J]. Thromb Vase Biol,1998; 18(11):1716-1722.
[29]Eguchiguchi Y, Keenton M, Loskutoff D. Endotoxin induces the expression of PAI-1 protein and mRNA by endothelial cells in mouse tissues in vivo[J]. Thromb Haemost,1994; 69(6):652-660.
[30]Ross R.The pathogenesis of atherosclerosis:a perspective for the 1990s[J]. Nature,1993; 362(29):801-809.
[31]Klinger KW, Winqvist R, Riccio A. Identification of regulatory sequences in type Ⅰ gene is located at region q21.3-q22 of chromosome 7 and genetically linked with cystic fibrosis[J]. Proc Natl Acad Sci USA,1987; 84:8548-8552.
[32]Kooistra T, yen den berg j, tons A. Butyrate stimulates tissue-type plasminogen-activator synthesis in cultured human endothelial cells[J]. Biochem J,1987; 247(3):605-612.
[33]Kreistensen PL, Larsson LI, Nielsen LS. Human endothelial cells contain one type of plasminogen activiator[J]. FEBS Lett,1984; 168:33-37.
[34]Sprengers ED, Akkerman JW, Jansen BG. Blood platelet plasminogen activator inhibitor:two different pools of endothelial cells type plasminogen activator inhibitor in human blood[J]. Thromb Haemost,1986; 55:325-329.
[35]Lupu F, Bergonzelli GE, Heim DA. Localization and production of plasminogen activator inhibitor-1 in human healthy and atherosclerotic arteries[J]. Arterioscler Thromb,1993; 13(7):1090-1100.
[36]Song Ren, Ricky Y.K.Maan, Aubie Angel. Oxidative modification enhances lipoprotein (a)-induced overproduction of plasminogen activator inhibitor-1 in cultured vascular endothelial cells[J]. Atherosclierosis,1997; 128:1-10.
[37]Arts, Jos G, Bosma PJ. Role of c-Jun and proximal phorbol 12-myristate-13-acetate-(PMA)-responsive elements in the regulation of basal and PMA-stimulated plasminogen-activator inhibitor-I gene expression in HepG2Eur[J]. Bio Chem,1996; 241:393-402.
[38]E.A.van den berg, E.D. Sprengers, M. Jaye. Regulation of plasminogen activator inhibitor-1 mRNA in human endotheliac cells[J]. Thromb Haemost,1988; 60(1):63-67.
[39]Nishimura H, Tsuji H, Masuda H. Angiotensin II increases plasminogen activator inhibitor-1 and tissue factor mRNA expression without changing that of tissue type plasminogen activator or tissue factor pathway inhibitor in cultured rat aortic endothelial cells[J]. Throm6 Haemost,1997; 77:1189-1195.
[40]Michael J, Niedala, Monica Stein-Picarella. Role of protein kinase C in tumor necrosis factor induction of endothelial cell urokinase-type plasminogen activator[J]. Blood,1993; 81(10):2608-2617.
[41]Carmeliet P, Moons L, Lijnen R. Inhibitory role of plasminogen activator inhibitor-1 in arterial wound healing and neointima formation:a gene targeting and gene transfer study in mice[J]. Circulation, 1997; 96(9):3180-3191.
[42]AAznar J, Estelles A, Tormo G. Plasminogen activator inhibitor activity and other fibrinolytic variables in patients with coronary artery disease[J]. Br Heart J,1988; 10:77-82.
[43]Huber K, lorg M, Probst P. A decrease in plasminogen activator-1 activity after successfulu percutaneous transluminal coronary angioplasty is associated with a significantly reduced risk for coronary restenosis[J]. Thromb Haemost,1992; 67:209-213.
[44]Wiman B, Hamsten A. The fibrinolytic enzyme system and its role in the etiology of thromboembolic disease[J]. Semin Thromb Hemost,1990; 16:207-216.
[45]Dawson S, Henney A. The status of PA1-1 as a risk factor for arterial and thrombotic.disease:A review[J]. Atherosclerosis,1992; 95:105-117.
[46]Schnciderman J, Sawdey MS, Keeton MR. Increased type 1 plasminogen activator inhibitor gene expression in atherosclerotic human arteries[J]. Proc Natl Acad Sci USA,1992; 89:6998-7002.
[47]Lemne. De Fair V Elevation of plasminogln activator inhibito-1 in borderline byepetensin is linked to concomitant metabolic disturbances[J]. Eur J Clin Invest,1996; 26(8):692.
[48]Erickson LA, Fici GJ, Lund JE, et al. Development of venous occlusions in mice transgenic for the plasminogen activator inhibitor-1 gene[J]. Nature,1990; 346(6279):74-76.
[49]Friederich PW, Levi M, Biemond BB, et al. Novel low-molecular-weight inhibitor of PAI-1 (XR5118)promotes endogenous fibrinolysis and reduces poslthromobolysis thrombus growth in rabbits[J]. Circulation,1997; 93(6):916-921.
[50]Francis RB, Kawanishi D, Baruch T, et al. Impaired fibrinolysis in coronary artery disease[J]. Am Heart J,1988; 115(4):776-780.
[51]Hua Y, XI G, Keep RF, et al. Plasminogen activator inhibitor-1 induction after experimental intracerebral hemorrhage[J]. J Cereb Blood Flow Metab,2002; 22(1):55-61.
[52]Festoff BW, Reddy RB, Van Becelaere M, et al. Activation of serpins and their cognate proteases in muscle after crush injury[J]. J Cell Physiol,1994; 159(1):11-18.
[53]Williams JJ, Moalli R, Calista C, et al. Pulmonary endothelial injury and altered fibrinolysis after femur fraeture in rabbits[J]. J Orthop Trauma,1990; 4(3):303-308.
[54]Aguirre BE, Yuste JR, Paramo JA, et al. Prevalence of hypercoagulation conditions in patients with thrombosis in Northern Navarra[J]. An Med Interna,1997; 14(9):450-454.
[55]Carmassi F, Morale M, Negri F, et al. Thrombin-antithrombin Ⅲ complexes as an additional diagnostic aid in pulmonary embolism[J]. Haemostasis,1996; 26(1):16-22.
[56]Huber K, Beckmann R, Frank H, et al. Fibrinogen, t-PA, and PAI-I plasma levels in patients with pulmonary hypertension[J]. Am J Respir Crit Care Med,1994; 150(4):929-933.
[57]Grimaudo V, Bachmann F, Hauert J, et al. Hypofibrinolysis in patients with a history of idiopathic deep vein thrombosis and/or pulmonary embolism[J]. Thromb Haemost,1992; 67(4):397-401.
[58]Wada H, Sakakura M, Nobori T, et al. Application of hemostatic molecular markers for diagnosis of thrombosis [J]. Rinsho Byori,2000; 48(4):301-307.
[59]Flores J, Garcia-Avello A, Flores VM, et al. Tissue plasminogen activator plasma levels as a potential diagnostic aid in acute pulmonary embolism[J]. Arch Pathol Lab Med,2003; 127(3):310-315.
[1]Titani K, Kumar S, Takio K, Ericsson LH, Wade RD, Ashida K, et al. Amino acid sequence of human von Willebrand factor. Biochemistry,1986; 25:31,71-84.
[2]Mangin PH, Receveur N, Wurtz V, et al. Identification of five novel 142323 isoforms interacting with the GPIb-IX complex in Platelets. Thromb Haemost[J],2009;24.
[3]Franchini M, Mannucci PM. Von Willebrand factonanother j anus-faced hemostasis protein. Semin Thromb Hemost,2008; 34 (7):663-669.
[4]Gonzales JU, Thistlethwaite JR, Thompson BC, et al. Exercise-induced shear stress is associated with changes in plasma von Willebrand factor in older humans. Eur J Appl Physiol,2009; 106(5):779-784.
[5]Hamaad A, Sosin MD, Blann AD, et al. M arkers of thrombosis and hemostasis in acute coronary syndromes:relationship to increased heart rate and reduced heart-rate variability. Clin Cardiol,2009; 32 (4):204-209.
[6]Bombeli T, Jutzi M, De Conne E, et al. In prtients with deep-vein thrombosis elevated levels of factor VIII correlate only with von Willebrand factor but not other endothelial cell-derived coagulation and fibrinolysis proteins. Blood Coagul Fibrinolysis,2002; 13(7):577-581.
[7]Navarro S, Ricart JM, Medina P, et al. Activated protein C levels in Behcet's disease and risk of venous thrombosis. Br J Haematol,2004; 126(4):550-556.
[8]Lytvyn CI, Kopitsa MP, petyunina OV. Interaction between inflammation and thrombosis in acute coronary syndrome. Kardiol Pol,2004; 61(8):110-116.
[9]Brooks EG, Trotman W, Wadsworth M P, et al.Valves of the deep venous system:an overlooked risk factor. Blood,2009; 114(6):1276-1279.
[10]Bongers TN, de Maat MP, van Goor ML, et al. High von Willebrand Factor Levels Increase the Risk of First Ischemic Stroke:influence of ADAM TS13,inflammation,and genetic vari-ability. Stroke,2006; 37(11):2672-2677.
[11]Girolami A, Tezza F, Scapin M, et al. Arterial and venous thrombosis in patients with von Willebrand's disease:a critical review of the literature. [J]Thromb Thrombolysis,2006; 21(2):175-178.
[12]Hough C, Cameron CL, Notley CR, et al. Influence of a GT repeat element on shear stress responsiveness of the VWF gene promoter.[J]Thromb Haemost,2008;6 (7):1183-1192.
[13]Hering S, Augustin C, Edelmann J, et al. Complex variability of intron 40 of the von Willebrand factor (vWF) gene. Int J Legal Med,2008; 122(1):67-71.
[14]Delange M, de Geus EJ, Kluft C, et al. Genetic influences on fibrongen, tissue plasminogen activator-antigen and von Willebrand factor in male and females. Thromb Haemost,2006; 95 (3):414-419.
[15]De Lange M, Snieder H, Ariens RA, et al.The genetics of haemostasis:a twin study. Lancet,2001; 357 (9250):101-105.
[16]Gallinaro L, Cattini MG, Sztukowska M, et al. A shorter von Willebrand factor survival in O blood group subjects explains how ABO determinants influence plasma von Willebrand factor. Blood,2008; 111(7):3540-3545.
[17]van Schooten CJ, Denis CV, Lisman T, et al. Variations in glycosylation of von Willebrand factor with O-linked sialylated Tantigen are associated with its plasma VWF levels. Blood,2007; 109(6):2430-2437.
[18]Katsouyanni K. Ambient air pollution and health. Br Med Bull,2003; 68:143-156.
[19]巫向前.临床检验结果的评价.北京,人民卫生出版社,2000；219-220.
[20]袁忠海,朱平.vWF基因单核苷酸多态性与血栓性疾病发病的关系.中国实验医学杂志,2010；18(2)：549-552.
[21]Titani K, Kumar S, Takio K, et al. Amino acid sequence of human von Willebrand Factor. Biochem, 1986; 25:3171.
[22]Shelto-Inloes BB, Titani K, Sadler JE. cDNA sequence for human von Willebrand Factor reveal five types of repeated domains and five possibleprotein sequence polymorphioms. Biochem,1986;25:3164.
[23]Wagner DD. Cell biology of von Willebrand factor.Ann Rev Cell Biol,1990; 6:217.
[24]Dent JA, Berkowitz SD, Ware J, et al. Identification of a cleavage site directing the immunochemical detection of molecular abnormalities in type A von Willebrand factor. Proc Natl Acad Sci USA,1990; 87:6306.
[25]Kaufman RJ, Wasley LC, Dorner AJ. Synthesis, processing, and secretion of recombinant human FactorⅧ expressed in mammalian cells. Biol Chem[J],1988; 263:6352.
[26]Barrow RT, Healey JF, Lollar P. Inhibition by hepar in of thrombin-catalyzed activation of the factor VIII-von Willebtand factor complex. Biol Chem[J],1994; 269:593.
[27]Arnason T, Wells PS,Forster AJ. Appropriateness of diagnostic strategies for evaluating suspected venous thromboembolism [J]. Thromb Haemost,2007; 97 (2):195-201.
[28]Thompson SG, Kienast J, Pyke SDM, et al. Hemostatic factors and the risk of myocardial infarction or sudden death in patientswith angina pectoris, european concerted action on thrombosis and disabilities angina pectoris study group[J]. N Engl J Med,1995; 332(10):635-641.
[29]Sakai H, Goto S, Kim JY, et al. Plasma concentration of von Willebrand factor in acute myocardial infarction [J]. Thromb Haemost,2000;84(2):204-209.
[30]马凤杰,宋书凯,许福亮等.血管性血友病因子在心脑血管疾病中的表现[J].潍坊医学院学报,2003；25(3)：184-186.
[31]Kozuka K, Kohriyama T, Nomura E, et al. Endothelial markers and adhesion molecules in acute ischemic stroke-sequential change and differences in stroke sub-type. Atherosclerosis[J],2002; 161(1):161-168.
[32]Kohriyama T, Yamaguchi S, Tanaka E, et al. Coagulation and fibrinolytic parameters as predictors for small-vessel disease revealed by magnetic resonance imaging of the brain[J].Rinsho Shinkeigaku,1996,36(5):640-647.
[33]Beuth W, Kasprzak H, Wozniak B, et al. Von willebrand factor in patient with subarachnoid hemorrhage[J]. Neurol Neurochirpol,2001; 35(5):130-134.
[34]Reininger AJ. vWF attributes-impact on thrombus formation[J].Thromb Res,2008; 122:S9-S13.
[35]Staelens S, Hadders MA, Vauterin S, et al. Paratope determination of the antithrombotic antibody 82D6A3 based on the crystal structure of its complex with the von Willebrand factor A3-domain [J]. J Biol Chem,2006; 281(4)2225-2231.
[36]Kageyama S, Yamamoto H, Nakazawa H, et al. Anti-human vWF monoclonal antibody, AJvW22Fab, inhibits repetitive coronary artery thrombosis without bleeding time prolongation in dogs[J]. Thromb Res,2001;101(5):395-404.
[37]Kageyama S, Yamamoto H, Nakazawa H, et al. Pharmacokinetics and pharmaco-dynamics of AJW200, a humanized monoclonal antibody to von Willebrand factor, in monkeys[J]. Arterioscler Thromb Vasc Biol,2002; 22(1):187-192.
[38]Fontayne A, Meiring M, Lamprecht S, et al. The humanized anti-glycop rotein Ibmonoclonal antibody h6B42Fab is a potent and safe antithrombotic in a high shear arterial thrombosis model in baboons [J]. Thromb Haemost,2008; 100(4):670-677.
[39]Gilbert JC, DeFeo-Fraulini T, Hutabarat RM, et al. First-in-human evaluation of anti-von Willebrand factor therapeutic aptamer ARC 1779 in healthy volunteers [J]. Circulation,2007; 116(23):2678-2686.
[2]Piovella F, Wang CJ, Lu H, et al. Deep-vein thrombosis rates after major orthopedic surgery in Asia. An epidemiological study based on postoperative screening with centrally adjudicated bilateral venography[J]. Thromb Haemost,2005; 3(12):2664-70.
[3]邱贵兴,戴尅戎,杨庆铭等.预防骨科大手术后深静脉血栓形成的专家建议--深静脉血栓形成预防座谈会纪要[J].中华骨科杂志.2005；25(10)：636-40.
[4]Cha SI, Lee SY, Kim CH, et al. Venous thromboembolism in Korean patients undergoing major orthopedic surgery:a prospective observational study using computed tomographic(CT) pulmonary angiography and indirect CT venography[J]. Korean Med Sci,2010,25(1):28-34.
[5]Byun SS, Kim JH, Kim YJ,et al. Evaluation of deep vein thrombosis with multidetector row CT after orthopedic arthroplasty:a prospective study for comparison with Doppler sonography[J]. Korean J Radiol,2008,9(1):59-66.
[6]付妍,王大为.血栓栓塞性疾病的急诊治疗和预防[J].中国临床医生,2006,34(8)：51-53.
[7]Lerman A,Zeiher AM. Endothelial function:cardiac events[J]. Circulation,2005,111(3):363-368.
[8]Chieko M, Hiroshi D, et al. Endothelial and Antithrombotic Actions of HDL[J]. Circ.Res,2006,98(4): 1352-1364.
[9]Zhi HY and Xiu FM. Recent Advances in Understanding Endothelial Dysfunction in Atherosclerosis[J]. CM&R,2006.
[10]Becker BF, Heindl B, Kupatt C, et al. Endothelial function and hemostasis[J]. Zeitschrift Fur Kardiologie,2000,89(3):160-167.
[11]Reitsma S, Oude Egbrink MG, Heijnen VV, et al. Endothelial glycocalyx thickness and platelet-vessel wall interactions during atherogenesis[J]. Thromb Haemost,2011,8(5):106.
[12]Zhou X, He P.Temporal and spatial correlation of platelet activating factor-induced increases in endothelial [Ca2+]i, nitric oxide, and gap formation in intact venules[J]. Am J Physiol Heart Circ Physiol,2011,13(1):198-209.
[13]Davignon J, Ganz P. Role of endothelial dysfunction in atherosclerosis[J]. Circulation,2004,109(4): 27-32.
[14]Polycystic ovarian syndrome and the risk of cardiovascular disease and thrombosis. Mak W Dokras A[J]. Semin Thromb Hemost,2009,35(7):613-620.
[15]Cohen AT, Agnelli G, Anderson FA, et al. Venous thromboembolism (VTE) in Europe. The number of VTE events and associated morbidity and mortality [J]. Thromb Haemost,2007,98(4):756-764.
[16]A1 Sayegh F, Almahmeed W, A1 Humood S, et al. Global Risk Profile Verification in Patients with Venous Thromboembolism (GRIP VTE) in 5 Gulf countries[J]. Clin Appl Thromb Hemost,2009, 15(3):289-296.
[17]John A. Heit. The Epidemiology of thromboembolism in the community[J], Arteriosclerosis, Thromb Vasc Biol,2008,28(3):370-372.
[18]Zakai NA, Wright J, Cushman M. Risk factors for venous thrombosis in medical inpatients:validation of a thrombosis risk score[J]. Thromb Haemost,2007; 2(12):2156-2161.
[19]Schellong SM. Complete compression ultrasound for the diagnosis of venous thromboembolism[J]. Curr Opin Pulm Med,2004; 10(5):350-355.
[20]Scarvelis D, Wells PS. Diagnosis and treatment of deep-vein thrombosis[J]. CMAJ,2006; 175(9): 1087-1092.
[21]Hacking NM, Hellewell A, Sadler P. Prevention of deep vein thrombosis and pulmonary embolus[J]. Anaesthesia and intensive care medicine,2006; 7(12):449-452.
[22]Pasternak RC, Criqui MH, Fowkes FG, et al. Atherosclerotic Vascular Disease Conference:Writing Group Ⅰ:epidemiology[J]. Circulation,2006; 109(21):2605-2612.
[23]Michell DL, Andrews KL, Woollard KJ, Chin-Dusting JP. Imaging leukocyte adhesion to the vascular endothelium at high intraluminal pressure[J]. Vis Exp,2011; (54).
[24]L. Batty. The incidence and timing of pulmonary embolism following major trauma[J]. Thrombosis Research,2009,40
[25]A.M. Tofigh, M. Karvandi, et al.Incidence and outcome of pulmonary embolism following popliteal venous repair in trauma cases [J]. British Medical Journal.2010.11.028.
[26]Anil Hingorani, Enrico Ascher, Natalia Markevich, et al.Risk factors for mortality in patients with upper extremity and internal jugular deep venous thrombosis [J].Journal of Vascular Surgery,2005, Vol.41 (3), pp.476-478.
[27]Cuc Mai,Daniel Hunt, et al.Upper-extremity Deep Venous Thrombosis:A Review [J].The American Journal of Medicine,2011 124(5):402-407.
[28]M.M.J. Beckers, H.J.T. Ruven, C.A. Seldenrijk, et al.Risk of thrombosis and infections of central venous catheters and totally implanted access ports in patients treated for cancer [J]. Thrombosis Research,2009,125 (4):318-321.
[29]Dominique Farge, Cecile Durant, Stephane Villiers, et al.Lessons from French national guidelines on the treatment of venous thrombosis and central venous catheter thrombosis in cancer patients [J]. Thrombosis Research,2010, Vol.125, pp.S108-S116.
[30]Popovic M, Smiljanic K, Dobutovic B,et al. Thrombin and vascular inflammation[J]. Mol Cell Biochem,2011.
[31]Chan, Wee-Shian, Spencer, Frederick A, Ginsberg, Jeffrey S, et al.Anatomic distribution of deep vein thrombosis in pregnancy [J]. Canadian Medical Association. Journal,2010, Vol.182 (7).
[32]Chan AK, Paredes N, et al.The coagulation system in humans[J]. Methods Mol Biol.2013;992:3-12.
[33]翟振国,王辰.肺栓塞-深静脉血栓形成的研究现状与展望.中国实用内科杂志,2006,10(14)：806-811
[34]Anil Hingorani, Enrico Ascher, Natalia Markevich, et al.Risk factors for mortality in patients with upper extremity and internal jugular deep venous thrombosis [J]. Journal of Vascular Surgery,2005, Vol.41 (3), pp.476-478
[35]Mark A. Jones, Dae Y. Lee, Jocelyn A. Segall, Gregory J. Landry, et al. Characterizing resolution of catheter-associated upper extremity deep venous thrombosis [J]. Journal of Vascular Surgery,2010, Vol.51 (1),pp.108-113.
[36]Engin Deniz Arslan, Suveyda Aksakalli Yesilaras, et al. Prediction of Pretest Probability Scoring Systems in Pulmonary Embolism:Wells, Kline and Geneva [J]. International Journal of Clinical Medicine,2013, Vol.03 (07), pp.731-735.
[37]B.M Wroblewski, Paul D Siney, Patricia A Fleming, et al. Fatal pulmonary embolism and mortality after revision of failed total hip arthroplasties [J]. The Journal of Arthroplasty,2000, Vol.15 (4), pp.437-439.
[38]Dellas C, Puls M, Lankeit M, et al. Elevated heart-type fatty acid-binding protein levels on admission predict an adverse outcome in normotensive patients with acute pulmonary embolism[J]. J Am Coll Cardiol 2010;55(19):2150-2157.
[39]Lankeit M, Kempf T, Dellas C, et al. Growth differentiation factor-15 for prognostic assessment of patients with acute pulmonary embolism[J]. Am J Respir Crit Care Med,2008,177(9):1018-1025
[40]Lankeit M, Konstantinides S.Thrombolysis for hemodynamically stable patients with pulmonary embolism:still searching for the intermediate-risk group[J]. Thromb Res,2009,124(6):647-648.
[41]Susan R. Kahn MD, MSc.The Post-thrombotic Syndrome:The Forgotten Morbidity of Deep Venous Thrombosis[J].Journal of Thrombosis and Thrombolysis,2006,21(1):41-48.
[42]Grewal, Nina K; Martinez, Jorge Trabal; et al.Quantity of clot lysed after catheter-directed thrombolysis for iliofemoral deep venous thrombosis correlates with postthrombotic morbidity[J].Journal of Vascular Surgery,2010,51, (5):1209-1214.
[43]Borjas L, Zabala W, et al. Intragenic polymorphisms of factor Ⅷ and Ⅸ genes and their utility in the indirect diagnosis of carriers of Haemophilias A and B[J]. Invest Clin.2010 Sep;51(3):391-401.
[44]Rachel T.Bond, Jacqueline M. Cohen, Anthony Comerota, et al. Surgical Treatment of Moderate-to-Severe Post-Thrombotic Syndrome[J]. Annals of Vascular Surgery, 2013,27(2):242-258.
[45]Giancarlo Agnelli, Cecilia Becattini. Acute Pulmonary Embolism[J].N Engl J Med 2010,363(4):266-274
[46]Mareike Lankeit,Stavros Konstantinides. Mortality Risk Assessment and the Role of Thrombolysis in Pulmonary Embolism[J].Clinics in Chest Medicine,2010,31(4):303-305.
[47]Mayor A, Hafiz A, Bassat Q, et al. Association of severe malaria outcomes with platelet-mediated clumping and adhesion to a novel host receptor[J]. PLoS One.2011,296(4):194-198.
[48]J.LATELLA, S.DESMARAIS, M.-J.MIRON,et al.Relation between D-dimer level, venous valvular reflux and the development of post-thrombotic syndrome after deep vein thrombosis[J]. Journal of Thrombosis and Haemostasis,2010,8(10):2169-2175.
[49]Kwiatkowski JN, Melchior A. Effects of fibroblast extracellular matrix calcification on platelet adhesion in vitro[J]. Platelets.2008 Sep;19(6):467-470.
[50]Ciltay EJ, Elber JMH, Fibrt CL, et al. Visceral fat accumulation is an important determinate of PAI-1 levels in young, nonbese men and woman modulation by cross-sex hormone administration[J]. Thromb Vase Biol,1998; 18(11):1716-1722.
[51]Eastwood KA, Vaughan A, McCune KH. Mesenteric vein thrombosis associated with anti-thrombin Ⅲ deficiency[J]. Ulster Med J.2009;78(1):53-55.
[52]Mayor A, Hafiz A, Bassat Q, et al. Association of severe malaria outcomes with platelet-mediated clumping and adhesion to a novel host receptor. PLoS One.2011;6(4):19422.
[53]Kwiatkowski JN, Melchior A. Effects of fibroblast extracellular matrix calcification on platelet adhesion in vitro. Platelets.2008;19(6):467-70.
[54]Spiroski I, Kedev S, Antov S,et al. Investigation of SERPINE1 genetic polymorphism in Macedonian patients with occlusive artery disease and deep vein thrombosis[J]. Kardiol Pol,2009; 67(10):1088-94.
[55]Lassila M, Fukami K, Jandeleit-Dahm K, et al. Plasminogen activator inhibitor-1 production is--pathogenetic in experimental murine diabetic renal disease[J]. Diabetologia,2007; 50(6):1315-1326.
[56]Kaplan JC, Kahn A & Chelly. Innegitimate transcription:tis use in the study of inherited desease[J]. Human Mutation,1992,1(3):357-360.
[57]Paul A Kyrle, Sabine Eichinger, Deep vein thrombosis[J]. The Lancet,2005,365(9465):1163-1174.
[58]Skliankina NN, Boldyreva NV, Shcheglovitova ON. Differences in functional activity of cultivated human vascular endothelium received from different donors[J]. Tsitologiia,2011,53(4):341-346.
[59]L6wenberg EC, Meijers JC, Levi M. Platelet-vessel wall interaction in health and disease[J]. Neth J Med,2010,68(6):242-251.
[60]Sandoo A, van Zanten JJ, et al. The endothelium and its role in regulating vascular tone[J]. Open Cardiovasc Med J,2010,23(4):302-312.
[61]His W. Die Haute und Hohlen des Korpers. Basel:Schwighauser,1865.
[62]Ross R, Glomset, JA (1973). Atherosclerosis and the arterial smooth muscle cell:proliferation of smooth muscle is a key event in the genesis of the lesions of atherosclerosis[J]. Science,180 (4093): 1332-1339.
[63]Furchgott RF, Zawadzki JV. the obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine[J].1980,288(5789):373-376.
[64]Maritza J, Prigent-Tessier A, Bagnost T, et al. Time course of vascular arginase expression and activity in spontaneously hypertensive rats[J]. Life Sci,2008,132(80):1128-1134.
[65]Santhanam L, Lim HK, Lim HK, et al. Inducible NO synthase dependent S-nitrosylation and activation of arginase1 contribute to age-related endothelial dysfunction[J]. Circ Res,2008,4(101): 692-702.
[66]Chandani Lewis, Sorenson JP, Richardson DM, et al. Mechanisms of aging-induced impairment of endothelium-dependent relaxation:role of tetrahydrobiopterin[J]. Am J Physiol Heart Circ Physiol, 2004,287(3):2448-2453.
[67]Nishimura H, Tsuji H, Masuda H. Angiotensin Ⅱ increases plasminogen activator inhibitor-1 and tissue factor mRNA expression without changing that of tissue type plasminogen activator or tissue factor pathway inhibitor in cultured rat aortic endothelial cells[J]. Throm Haemost,1997,77(6):1189-1195.
[68]Bizzozer, et al.function of platelet. Blood Coagul Fibrinolysis.1881.
[69]Hoffman M, Monroe DM, Roberts HR. Activated factor Ⅶ activates factors Ⅸ and Ⅹ on the surface of activated platelets:thoughts on the mechanism of action of high-dose activated factor ⅦVII[J].. Blood Coagul Fibrinolysis.1998,9 (suppl 1):S61-S65.
[70]Gnatenko DV, Saenko EL, Jesty J, et al. Human factor Ⅷ can be packaged and functionally expressed in an adenoassociated virus background:applicability to haemophilia A gene therapy [J]. Br J Haematol,1999,104(3):27-36.
[71]Cole VJ, Staton JM, Eikelboom JW, et al. Collagen platelet receptor polymorphisms integrin alpha-betal C807T and GPVI Q317L and risk of ischemic stroke[J].. J Thromb Haemost.2003,27(1): 963-970.
[72]Jackson SP, Nesbitt WS, Kulkarni S. Signaling events underlying thrombus formation[J]. J Thromb Haemost.2003,28(1):1602-1612.
[73]Kuijpers, M. J. E, Schulte, V, Bergmeier, W, et al. Complementary roles of glycoprotein VI and alpha-betal integrin in collagen-induced thrombus formation in flowing whole blood ex vivo[J]. FASEB J,17(3):685-687.
[74]Peter C, et al. Recent Advances in Understanding platelet Dysfunction in thrombosis [J]. Blood,2003, 32(4):314-351.
[75]Hidenori K, et al. Mechanisms of the platelet incoronary artery disease [J]. Arterioscler Thromb Vase Biol,2013,28(1):1672-1677.
[76]Goto S, Tamura N, Ishida H. Ability of anti-glycoprotein Ⅱb/Ⅲa agents to dissolve platelet thrombi formed on a collagen surface under blood flow conditions[J]. J Am Coll Cardiol,2004,44(3): 316-323.
[77]Bigalke B, Stellos K, Geisler T, et al. High plasma levels o adipocytokines are associated with platelet activation in patients with coronary artery disease[J]. Platelets.2010,21(1):11-19.
[78]GC Parry, N Mackman. A set of inducible genes expressed by activated human monocytic and endothelial cells contain kappa B-like sites that specifically bind c-Rel-p65 heterodimers. Journal of Biological Chemistry[J],1994,37(6):12-17.
[79]Harry Holzmuller, Thoma Moll, Renate Hofer-Warbinek, et al. A Transcriptional Repressor of the Tissue Factor Gene in Endothelial Cells[J]. Arteriosclerosis, Thrombosis, and Vascular Biology,1999, 19(3):1804-1811.
[80]Sumanta Mukherjee, Sanjay K Banerjee, Mohua Maulik, et al. Protection against acute adriamycin-induced cardiotoxicity by garlic:Role of endogenous antioxidants and inhibition of TNF-a expression[J]. BMC Pharmacology,2003,15(3):16-21.
[81]Zhi HY, Xiu FM. Recent Advances in Understanding Endothelial Dysfunction in Atherosclerosis[J]. CM&R,2006,17(4):189-194.
[82]Jude B, Zawadzki C, Susen S, et al. Relevance of tissue factor in cardiovascular disease[J].2005, 98(6):667-671.
[83]Eduardo Ramacciottia, Angela E.Hawleya, Shirley K, et al. Proteomics of microparticles after deep venous thrombosis[J]. Thrombosis Research,2010,125(6):123-138.
[84]Nilius B, Droogmans G. Ion channels and their functional role in vascular endothelium[J]. Physiol Rev, 2001; 81 (4):1415-59.
[85]Venturini CM, Weston LK, Kaplan JE. Platelet cGMP, but not cAMP, inhibits thrombin-induced platelet adhesion to pulmonary vascular endothelium[J]. Am J Physiol,1992,263(3):606-612.
[86]Popovic M, Smiljanic K, Dobutovic B, et al. Thrombin and vascular inflammation[J]. Mol Cell Biochem,2011,47(3):81-90.
[87]Hollenberg MD, Laniyonu AA, Saifeddine M, et al. Role of the amino- and carboxyl-terminal domains of thrombin receptor-derived polypeptides in biological activity in vascular endothelium and gastric smooth muscle:evidence for receptor subtypes[J]. Mol Pharmacol,1993,43(6):921-930.
[88]Hiroaki N, Hisanori H, et al. Small GTPase Rho Regulates Thrombin-Induced Platelet Aggregation[J]. Biochemical and Biophysical Research Communications,2001,280(5):970-975.
[89]Schneppenheim R, Budde U. von Willebrand factor:the complex molecular genetics of a multidomain and multifunctional protein[J]. Thromb Haemost,2011,37(1):209-215.
[90]Tsantes AE, Nikolopoulos GK, Tsirigotis P, et al. Direct evidence for normalization of platelet function resulting from platelet count reduction in essential thrombocythemia[J]. Blood Coagul Fibrinolysis,2011,22(6):457-462.
[91]Armin J. Reininger. VWF attributes impact on thrombus formation[J]. Thrombosis research,2008, 122(4):S9-S13.
[92]Van Stralen KJ, et al. Mechanisms of the Factor V Leiden Paradox[J]. Arterioscler Thromb Vasc Biol, 2008,28(2):1872-1877.
[93]Brouwer JL, Bijl M, Veeger, NJ, et al. The contribution of inherited and acquired thrombophilic defects, alone or combined with antiphospholipid antibodies, to venous and arterial thromboembolism in patients with systemic lupus erythematosus[J]. Blood,2004,104(7):143-148.
[94]周欢琴,谢海宝,肖震等,检测血浆uPA、uPAR、t-PA和PAI-1水平在缺血性心脑血管疾病发病中的意义[J],浙江检验医学,2007,4(7)：32-39.
[95]郑美琴,林燕,李宝清等,脑梗死患者血浆vWF、PLG、D-D含量变化与临床意义[J].现代实用医学,2006,9(6)：45-49.
[96]程彦,胡厚源.血小板膜糖蛋白GP Ⅰbα拮抗剂的研究进展[J].心血管病学进展,2013；5(1)：67-69.
[97]阳艾珍,王璐,周俊松.Tyro 3受体酪氨酸激酶调控糖蛋白Ⅵ介导的血小板活化,血栓与止血学,2012；3(02)：354-358.
[98]K L Moore, K D Patel, R E Bruehl, F Li, et al. P-selectin glycoprotein ligand-1 mediates rolling of human neutrophils on P-selectin[J]. Moore et al.128 (4):661.
[99]Robert C. Fuhlbrigge2, J. David Kieffer2, et al. Cutaneous lymphocyte antigen is a specialized form of PSGL-1 expressed on skin-homing T cells[J]. Nature,1997;17(2):978-981.
[100]庄旭琴,霍建丽,杨天雨,等.血小板ADP受体及其拮抗剂的研究进展[J].药物生物技术,2010；32(16)：368-371.
[101]Biochemistry Department, J. H. Holland Laboratory, American Red Cross, et al. The serpin PAI-1 inhibits cell migration by blocking integrin αvβ3 binding to vitronectin[J].Nature 383,441-443.
[102]Feng,Gullans SR.Connecting the dots using gene-expression profiles. The New England journal of medicine 2006;355 (19):2042-2042.
[103]Haley, Dohner K, Bair E, Use of gene-expression profiling to identify prognostic subclasses in adult acute myeloid leukemia. The New England journal of medicine 2004 Apr; 350 (16):1605-16.
[104]Chen X Molecular cloning,characterization and expression of cDNA encoding translatonally controlled tumor protein (TCTP) from Jatropha curcas L.Mol Biol Rep.2011 V38N5:3107
[105]Yajima, Hertel PM, Estes MK, Vaccine-acquired rotavirus in infants with severe combined immunodeficiency. The New England journal of medicine 2010 Jan; 362 (4):314-9.
[106]Takeya M, Yamasaki F, Uzuhashi S, NIASGBdb:NIAS Genebank databases for genetic resources and plant disease information. Nucleic acids research 2011 Jan; 39
[107]Yang YS, Song HD, The gene expression profiling of sporadic pheochromocytoma and novel full-length cDNAs cloning. Endocrine-related cancer 2003 Dec; 10 (4):621-7
[108]Van Hintum TJ, Van Treuren R. Molecular markers:tools to improve genebank efficiency. Cellular & molecular biology letters 2002; 7 (2B):737-44.
[109]Chen CL, Liu IH, Fliesler SJ, et al. Cholesterol suppresses cellular TGF-beta responsiveness: implications in atherogenesis[J]. Cell Sci,2007; 120:3509-3521.
[110]Gonzales JU, Thistlethwaite JR, Thompson BC, et al. Exercise-induced shear stress is associated with changes in plasma von Willebrand factor in older humans. Eur J Appl Physiol,2009; 106(5) 779-784.
[111]Jiang M, Zhao Y, Shen F, et al. Epitope mapping of human VWF A3 recognized by monoclonal antibody SZ-123 and SZ-125 using MALDI mass spectrometry[J]. Int J Hematol.2011;94(3):241-7.
[112]Law RH, Zhang QW, McGowan S, et al. An overview of the Serpin superfamily[J]. Genome Biol, 2006; 7(5):216-220.
[113]Izuhara K, Ohta S, Kanaji S, et al. Recent progress in understanding the diversity of the human ov-Serpin/cladeB Serpin family[J]. Cellular and molecular life sciences,2008,65(16):2541-2553.
[114]Lhermusier T, Van Rottem J, Garcia C, et al. The Syk-Kinase Inhibitor R406 Impairs Platelet Activation and Monocyte Tissue Factor Expression Triggered by Heparin-PF4 Complex Directed Antibodies[J]. Thromb Haemost,2011,65(16):341-353.
[115]Rohan Samarakoonl, Subhanir S. Redox-Induced Src Kinase and Caveolin-1 Signaling in TGF-b1-Initiated SMAD2/3 Activation and PAI-1 Expression[J]. PLoS ONE,6(7):273-284.
[116]Vladimir Leksa, Samuel Godar, et al. TGF-1-induced apoptosis in endothelial cells mediated by M6P/IGFII-R and mini-plasminogen[J]. Journal of Cell Science,118(7):4577-4586.
[117]Rohan Samarakoon, Stephen P. Higgins, et al. TGF-bl-induced plasminogen activator inhibitor-1 expression in vascular smooth muscle cells requires pp60c-src/EGFRY845 and Rho/ROCK signaling[J]. J Mol Cell Cardiol,2008,44(3):527-538.
[118]Marie-Jose Goumansl, Zhen Liu, Peter ten Dijkel, et al.TGF-b signaling in vascular biology and dysfunction[J]. Cell Research,2009,19(3):116-127.
[119]Rohan Samarakoon and Paul J. Higgins, et al.Integration of non-SMAD and SMAD signaling in TGF-β1-induced plasminogen activator inhibitor type-1 gene expression in vascular smooth muscle cells[J]. Thromb Haemost,2008,100(6):976-983.
[120]Hough C, Cameron CL, Notley CR, et al. Influence of a GT repeat element on shear stress responsiveness of the VWF gene promoter[J]. Thromb Haemost,2008,6 (7):1183-1192.
[121]Izuhara K, Ohta S, Kanaji S, et al. Recent progress in understanding the diversity of the human ov-Serpin/cladeB Serpin family[J]. Cellular and molecular life sciences,2008,65(16):2541-2553.
[1]Mangan MS, Kaiserman D, Bird PI. The role of Serpin in vertebrate immunity[J]. Tissue Antigens, 2008;72(1):1-10.
[2]张雷,唐瞻贵,仝向娟.丝氨酸蛋白酶抑制剂和血管内皮生长因子基因在口腔鳞癌中的表达[J].2004；39(5)：420.
[3]曾蕾,曹江,张行.丝氨酸蛋白酶SNC19及其抑制因子在胃癌中的表达[J].中华消化杂志,2004；24(7)：429-430.
[4]Irving JA, Pike RN, Lesk AM, et al. Phylogeny of the Serpin superfamily:implications of patterns of amino acid conservation for structure and function[J]. Genome Res,2000; 10:1845-1864.
[5]Law RH, Zhang QW, McGowan S, et al. An overview of the Serpin superfamily[J]. Genome Biol, 2006; 7(5):216-220.
[6]戚正武.丝氨酸蛋白酶抑制剂的结构与功能[J].生物化学与生物物理进展,1998；15(5)：322-329.
[7]Krowarsch D, Cierpicki T, Jelen F, et al. Canonical protein inhibitors of serine proteases[J]. Cell Mol Life Sci,2003; 60(11):2427-2444.
[8]Gary AS, Phillip IB, Robin WC, et al. The Serpin are an expanding superfamily of structurally similar but functionally diverse proteins[J]. Biological Chmistry,2001; 276(36):33293-33296.
[9]Molnar K, Holderith BN, Csikos G, et al. Distribution of Serpin in the tissues of the tobacco hornworm(Manduca sexta)larvae:Existence of new Serpin possibly encoded by a gene distinct from the Serpin-1 gene[J]. Insect Physiol,2001,47(7):675-687.
[10]Izuhara K, Ohta S, Kanaji S, et al. Recent progress in understanding the diversity of the human ov-Serpin/cladeB Serpin family[J]. Cellular and molecular life sciences,2008,65(16):2541-2553.
[11]Diana VG, Paul S, Kevin M, et al. Serpin:structure, function and molecular evolution[J]. Biochemistry & Cell Biology,2003; 35:1536-1547.
[12]Li W, Johnson DJ, Esmon CT, Huntington JA. Structure of the antithrombin-thrombin-heparin ternary complex reveals the antithrombotic mechanism of heparin[J]. Nat Struct Mol Biol,2004; 11:857-862.
[13]Kounnas MZ, Church FC, Argraves WS, et al. Cellular internalization and degradation of antithrombin Ⅲ-thrombin, heparin cofactor Ⅱ-thrombin, and alpha 1-antitrypsintrypsin complexes is mediated by the low density lipoprotein receptor-related protein[J]. Biol Chem,1996; 271:6523-6529.
[14]张曙光.中国林蛙皮肤丝氨酸蛋白酶抑制剂RCSP12的基因克隆和原核表达[J].水生生物学报,2010；34(03).
[15]Izuhara K, Ohta S, Kanaji S, et al. Recent progress in understanding the diversity of the human ov-Serpin/cladeB Serpin family[J]. Cellular and molecular life sciences,2008; 65(16):2541-2553.
[16]汪世华,王文勇,黄益洲.丝氨酸蛋白酶研究进展[J].福建农业学报,2007；22(4)：453-456.
[17]Mangan MS, Kaiserman D, Bird PI. The role of Serpin in vertebrate immunity[J]. Tissue Antigens, 2008;72(1):1-10.
[18]Pemberton PA, Stein PE, Pepys MB, et al. Hormone binding globulins undergo Serpin conformational change in inflammation[J]. Nature,1988; 336:257-258.
[19]Zou Z, Anisowicz A, Hendrix MJ, et al. A Serpin with tumor-suppressing activity in human mammary epithelial cells[J]. Science,1994; 263:526-529.
[20]Nagata K. Hsp47:a collagen-specific molecular chaperone[J]. Trends Biochem Sci,1996; 21:22-26.
[21]Lomas DA, Evans DL, Finch JT, et al. The mechanism of Zalpha 1-antitrypsin accumulation in the liver[J]. Nature,1992; 357:605-607.
[22]Bruce D, Perry DJ, Borg JY, et al. Thromboembolic disease due to thermolabile conformational changes of antithrombin Rouen-VI(187 Asn→Asp)[J].Clin Invest,1994; 94:2265-2274.
[23]Aulak KS, Pemberton PA, Rosen FS, et al. Dysfunctional C1-inhibitor(At), isolated from a type Ⅱ hereditary-angio-oedema plasma, contains a P1 'reactive centre'(Arg444→His) mutation[J]. J Biochem,1988; 253:615-618.
[24]Davis RL, Shrimpton AE, Holohan PD, et al. Familial dementia caused by polymerization of mutant neuroSerpin[J]. Nature,1999; 401:376-379.
[25]Stein PE, Carrell RW. What do dysfunctional Serpin tell us about molecular mobility and disease?[J]. Nat Struct Biol,1995; 2:96-113.
[26]Mehta J.L, D.Y.Li. Identification and autoregulation of receptor for ox-LDL in cultured human coronary artery endothelial cells[J]. Brioche Biophysical Res Comm,1998; 248:511-514.
[27]Mourik V, Lawrence DA, Loskutoff DJ. Purification of an inhibitor of plasminogen activator(antiactivator)synthesized by endothelial cells[J]. Biol Chem,1984; 259(23):14914-14921.
[28]Ciltay EJ, Elber JMH, Fibrt CL, et al. Visceral fat accumulation is an important determinate of PAI-1 levels in young, nonbese men and woman modulation by cross-sex hormone administration[J]. Thromb Vase Biol,1998; 18(11):1716-1722.
[29]Eguchiguchi Y, Keenton M, Loskutoff D. Endotoxin induces the expression of PAI-1 protein and mRNA by endothelial cells in mouse tissues in vivo[J]. Thromb Haemost,1994; 69(6):652-660.
[30]Ross R.The pathogenesis of atherosclerosis:a perspective for the 1990s[J]. Nature,1993; 362(29):801-809.
[31]Klinger KW, Winqvist R, Riccio A. Identification of regulatory sequences in type Ⅰ gene is located at region q21.3-q22 of chromosome 7 and genetically linked with cystic fibrosis[J]. Proc Natl Acad Sci USA,1987; 84:8548-8552.
[32]Kooistra T, yen den berg j, tons A. Butyrate stimulates tissue-type plasminogen-activator synthesis in cultured human endothelial cells[J]. Biochem J,1987; 247(3):605-612.
[33]Kreistensen PL, Larsson LI, Nielsen LS. Human endothelial cells contain one type of plasminogen activiator[J]. FEBS Lett,1984; 168:33-37.
[34]Sprengers ED, Akkerman JW, Jansen BG. Blood platelet plasminogen activator inhibitor:two different pools of endothelial cells type plasminogen activator inhibitor in human blood[J]. Thromb Haemost,1986; 55:325-329.
[35]Lupu F, Bergonzelli GE, Heim DA. Localization and production of plasminogen activator inhibitor-1 in human healthy and atherosclerotic arteries[J]. Arterioscler Thromb,1993; 13(7):1090-1100.
[36]Song Ren, Ricky Y.K.Maan, Aubie Angel. Oxidative modification enhances lipoprotein (a)-induced overproduction of plasminogen activator inhibitor-1 in cultured vascular endothelial cells[J]. Atherosclierosis,1997; 128:1-10.
[37]Arts, Jos G, Bosma PJ. Role of c-Jun and proximal phorbol 12-myristate-13-acetate-(PMA)-responsive elements in the regulation of basal and PMA-stimulated plasminogen-activator inhibitor-I gene expression in HepG2Eur[J]. Bio Chem,1996; 241:393-402.
[38]E.A.van den berg, E.D. Sprengers, M. Jaye. Regulation of plasminogen activator inhibitor-1 mRNA in human endotheliac cells[J]. Thromb Haemost,1988; 60(1):63-67.
[39]Nishimura H, Tsuji H, Masuda H. Angiotensin II increases plasminogen activator inhibitor-1 and tissue factor mRNA expression without changing that of tissue type plasminogen activator or tissue factor pathway inhibitor in cultured rat aortic endothelial cells[J]. Throm6 Haemost,1997; 77:1189-1195.
[40]Michael J, Niedala, Monica Stein-Picarella. Role of protein kinase C in tumor necrosis factor induction of endothelial cell urokinase-type plasminogen activator[J]. Blood,1993; 81(10):2608-2617.
[41]Carmeliet P, Moons L, Lijnen R. Inhibitory role of plasminogen activator inhibitor-1 in arterial wound healing and neointima formation:a gene targeting and gene transfer study in mice[J]. Circulation, 1997; 96(9):3180-3191.
[42]AAznar J, Estelles A, Tormo G. Plasminogen activator inhibitor activity and other fibrinolytic variables in patients with coronary artery disease[J]. Br Heart J,1988; 10:77-82.
[43]Huber K, lorg M, Probst P. A decrease in plasminogen activator-1 activity after successfulu percutaneous transluminal coronary angioplasty is associated with a significantly reduced risk for coronary restenosis[J]. Thromb Haemost,1992; 67:209-213.
[44]Wiman B, Hamsten A. The fibrinolytic enzyme system and its role in the etiology of thromboembolic disease[J]. Semin Thromb Hemost,1990; 16:207-216.
[45]Dawson S, Henney A. The status of PA1-1 as a risk factor for arterial and thrombotic.disease:A review[J]. Atherosclerosis,1992; 95:105-117.
[46]Schnciderman J, Sawdey MS, Keeton MR. Increased type 1 plasminogen activator inhibitor gene expression in atherosclerotic human arteries[J]. Proc Natl Acad Sci USA,1992; 89:6998-7002.
[47]Lemne. De Fair V Elevation of plasminogln activator inhibito-1 in borderline byepetensin is linked to concomitant metabolic disturbances[J]. Eur J Clin Invest,1996; 26(8):692.
[48]Erickson LA, Fici GJ, Lund JE, et al. Development of venous occlusions in mice transgenic for the plasminogen activator inhibitor-1 gene[J]. Nature,1990; 346(6279):74-76.
[49]Friederich PW, Levi M, Biemond BB, et al. Novel low-molecular-weight inhibitor of PAI-1 (XR5118)promotes endogenous fibrinolysis and reduces poslthromobolysis thrombus growth in rabbits[J]. Circulation,1997; 93(6):916-921.
[50]Francis RB, Kawanishi D, Baruch T, et al. Impaired fibrinolysis in coronary artery disease[J]. Am Heart J,1988; 115(4):776-780.
[51]Hua Y, XI G, Keep RF, et al. Plasminogen activator inhibitor-1 induction after experimental intracerebral hemorrhage[J]. J Cereb Blood Flow Metab,2002; 22(1):55-61.
[52]Festoff BW, Reddy RB, Van Becelaere M, et al. Activation of serpins and their cognate proteases in muscle after crush injury[J]. J Cell Physiol,1994; 159(1):11-18.
[53]Williams JJ, Moalli R, Calista C, et al. Pulmonary endothelial injury and altered fibrinolysis after femur fraeture in rabbits[J]. J Orthop Trauma,1990; 4(3):303-308.
[54]Aguirre BE, Yuste JR, Paramo JA, et al. Prevalence of hypercoagulation conditions in patients with thrombosis in Northern Navarra[J]. An Med Interna,1997; 14(9):450-454.
[55]Carmassi F, Morale M, Negri F, et al. Thrombin-antithrombin Ⅲ complexes as an additional diagnostic aid in pulmonary embolism[J]. Haemostasis,1996; 26(1):16-22.
[56]Huber K, Beckmann R, Frank H, et al. Fibrinogen, t-PA, and PAI-I plasma levels in patients with pulmonary hypertension[J]. Am J Respir Crit Care Med,1994; 150(4):929-933.
[57]Grimaudo V, Bachmann F, Hauert J, et al. Hypofibrinolysis in patients with a history of idiopathic deep vein thrombosis and/or pulmonary embolism[J]. Thromb Haemost,1992; 67(4):397-401.
[58]Wada H, Sakakura M, Nobori T, et al. Application of hemostatic molecular markers for diagnosis of thrombosis [J]. Rinsho Byori,2000; 48(4):301-307.
[59]Flores J, Garcia-Avello A, Flores VM, et al. Tissue plasminogen activator plasma levels as a potential diagnostic aid in acute pulmonary embolism[J]. Arch Pathol Lab Med,2003; 127(3):310-315.
[1]Titani K, Kumar S, Takio K, Ericsson LH, Wade RD, Ashida K, et al. Amino acid sequence of human von Willebrand factor. Biochemistry,1986; 25:31,71-84.
[2]Mangin PH, Receveur N, Wurtz V, et al. Identification of five novel 142323 isoforms interacting with the GPIb-IX complex in Platelets. Thromb Haemost[J],2009;24.
[3]Franchini M, Mannucci PM. Von Willebrand factonanother j anus-faced hemostasis protein. Semin Thromb Hemost,2008; 34 (7):663-669.
[4]Gonzales JU, Thistlethwaite JR, Thompson BC, et al. Exercise-induced shear stress is associated with changes in plasma von Willebrand factor in older humans. Eur J Appl Physiol,2009; 106(5):779-784.
[5]Hamaad A, Sosin MD, Blann AD, et al. M arkers of thrombosis and hemostasis in acute coronary syndromes:relationship to increased heart rate and reduced heart-rate variability. Clin Cardiol,2009; 32 (4):204-209.
[6]Bombeli T, Jutzi M, De Conne E, et al. In prtients with deep-vein thrombosis elevated levels of factor VIII correlate only with von Willebrand factor but not other endothelial cell-derived coagulation and fibrinolysis proteins. Blood Coagul Fibrinolysis,2002; 13(7):577-581.
[7]Navarro S, Ricart JM, Medina P, et al. Activated protein C levels in Behcet's disease and risk of venous thrombosis. Br J Haematol,2004; 126(4):550-556.
[8]Lytvyn CI, Kopitsa MP, petyunina OV. Interaction between inflammation and thrombosis in acute coronary syndrome. Kardiol Pol,2004; 61(8):110-116.
[9]Brooks EG, Trotman W, Wadsworth M P, et al.Valves of the deep venous system:an overlooked risk factor. Blood,2009; 114(6):1276-1279.
[10]Bongers TN, de Maat MP, van Goor ML, et al. High von Willebrand Factor Levels Increase the Risk of First Ischemic Stroke:influence of ADAM TS13,inflammation,and genetic vari-ability. Stroke,2006; 37(11):2672-2677.
[11]Girolami A, Tezza F, Scapin M, et al. Arterial and venous thrombosis in patients with von Willebrand's disease:a critical review of the literature. [J]Thromb Thrombolysis,2006; 21(2):175-178.
[12]Hough C, Cameron CL, Notley CR, et al. Influence of a GT repeat element on shear stress responsiveness of the VWF gene promoter.[J]Thromb Haemost,2008;6 (7):1183-1192.
[13]Hering S, Augustin C, Edelmann J, et al. Complex variability of intron 40 of the von Willebrand factor (vWF) gene. Int J Legal Med,2008; 122(1):67-71.
[14]Delange M, de Geus EJ, Kluft C, et al. Genetic influences on fibrongen, tissue plasminogen activator-antigen and von Willebrand factor in male and females. Thromb Haemost,2006; 95 (3):414-419.
[15]De Lange M, Snieder H, Ariens RA, et al.The genetics of haemostasis:a twin study. Lancet,2001; 357 (9250):101-105.
[16]Gallinaro L, Cattini MG, Sztukowska M, et al. A shorter von Willebrand factor survival in O blood group subjects explains how ABO determinants influence plasma von Willebrand factor. Blood,2008; 111(7):3540-3545.
[17]van Schooten CJ, Denis CV, Lisman T, et al. Variations in glycosylation of von Willebrand factor with O-linked sialylated Tantigen are associated with its plasma VWF levels. Blood,2007; 109(6):2430-2437.
[18]Katsouyanni K. Ambient air pollution and health. Br Med Bull,2003; 68:143-156.
[19]巫向前.临床检验结果的评价.北京,人民卫生出版社,2000；219-220.
[20]袁忠海,朱平.vWF基因单核苷酸多态性与血栓性疾病发病的关系.中国实验医学杂志,2010；18(2)：549-552.
[21]Titani K, Kumar S, Takio K, et al. Amino acid sequence of human von Willebrand Factor. Biochem, 1986; 25:3171.
[22]Shelto-Inloes BB, Titani K, Sadler JE. cDNA sequence for human von Willebrand Factor reveal five types of repeated domains and five possibleprotein sequence polymorphioms. Biochem,1986;25:3164.
[23]Wagner DD. Cell biology of von Willebrand factor.Ann Rev Cell Biol,1990; 6:217.
[24]Dent JA, Berkowitz SD, Ware J, et al. Identification of a cleavage site directing the immunochemical detection of molecular abnormalities in type A von Willebrand factor. Proc Natl Acad Sci USA,1990; 87:6306.
[25]Kaufman RJ, Wasley LC, Dorner AJ. Synthesis, processing, and secretion of recombinant human FactorⅧ expressed in mammalian cells. Biol Chem[J],1988; 263:6352.
[26]Barrow RT, Healey JF, Lollar P. Inhibition by hepar in of thrombin-catalyzed activation of the factor VIII-von Willebtand factor complex. Biol Chem[J],1994; 269:593.
[27]Arnason T, Wells PS,Forster AJ. Appropriateness of diagnostic strategies for evaluating suspected venous thromboembolism [J]. Thromb Haemost,2007; 97 (2):195-201.
[28]Thompson SG, Kienast J, Pyke SDM, et al. Hemostatic factors and the risk of myocardial infarction or sudden death in patientswith angina pectoris, european concerted action on thrombosis and disabilities angina pectoris study group[J]. N Engl J Med,1995; 332(10):635-641.
[29]Sakai H, Goto S, Kim JY, et al. Plasma concentration of von Willebrand factor in acute myocardial infarction [J]. Thromb Haemost,2000;84(2):204-209.
[30]马凤杰,宋书凯,许福亮等.血管性血友病因子在心脑血管疾病中的表现[J].潍坊医学院学报,2003；25(3)：184-186.
[31]Kozuka K, Kohriyama T, Nomura E, et al. Endothelial markers and adhesion molecules in acute ischemic stroke-sequential change and differences in stroke sub-type. Atherosclerosis[J],2002; 161(1):161-168.
[32]Kohriyama T, Yamaguchi S, Tanaka E, et al. Coagulation and fibrinolytic parameters as predictors for small-vessel disease revealed by magnetic resonance imaging of the brain[J].Rinsho Shinkeigaku,1996,36(5):640-647.
[33]Beuth W, Kasprzak H, Wozniak B, et al. Von willebrand factor in patient with subarachnoid hemorrhage[J]. Neurol Neurochirpol,2001; 35(5):130-134.
[34]Reininger AJ. vWF attributes-impact on thrombus formation[J].Thromb Res,2008; 122:S9-S13.
[35]Staelens S, Hadders MA, Vauterin S, et al. Paratope determination of the antithrombotic antibody 82D6A3 based on the crystal structure of its complex with the von Willebrand factor A3-domain [J]. J Biol Chem,2006; 281(4)2225-2231.
[36]Kageyama S, Yamamoto H, Nakazawa H, et al. Anti-human vWF monoclonal antibody, AJvW22Fab, inhibits repetitive coronary artery thrombosis without bleeding time prolongation in dogs[J]. Thromb Res,2001;101(5):395-404.
[37]Kageyama S, Yamamoto H, Nakazawa H, et al. Pharmacokinetics and pharmaco-dynamics of AJW200, a humanized monoclonal antibody to von Willebrand factor, in monkeys[J]. Arterioscler Thromb Vasc Biol,2002; 22(1):187-192.
[38]Fontayne A, Meiring M, Lamprecht S, et al. The humanized anti-glycop rotein Ibmonoclonal antibody h6B42Fab is a potent and safe antithrombotic in a high shear arterial thrombosis model in baboons [J]. Thromb Haemost,2008; 100(4):670-677.
[39]Gilbert JC, DeFeo-Fraulini T, Hutabarat RM, et al. First-in-human evaluation of anti-von Willebrand factor therapeutic aptamer ARC 1779 in healthy volunteers [J]. Circulation,2007; 116(23):2678-2686.