Plasminogen activator inhibitor-1 and vitronectin promote vascular thrombosis in mice

作     者：Eitzman, DT Westrick, RJ Nabel, EG Ginsburg, D 

作者机构：Univ Michigan Med Ctr Cardiovasc Res Ctr Ann Arbor MI 48109 USA Univ Michigan Med Ctr Dept Internal Med Div Mol Med & Human Genet Ann Arbor MI 48109 USA Univ Michigan Med Ctr Howard Hughes Med Inst Ann Arbor MI 48109 USA 

出 版 物：《BLOOD》 (血液)

年 卷 期：2000年第95卷第2期

页      面：577-580页

核心收录：

学科分类：1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

基　　金：NHLBI NIH HHS [HL03695-02  HL57345] Funding Source: Medline 

主　　题：颈动脉狭窄/血液 颈动脉狭窄/遗传学 颈动脉狭窄/病理生理学 颈静脉 小鼠 近交C57BL 小鼠 基因敲除 纤溶酶原激活物抑制物1/缺乏 纤溶酶原激活物抑制物1/遗传学 纤溶酶原激活物抑制物1/生理学 血栓形成/血液 血栓形成/遗传学 血栓形成/病理生理学 静脉血栓形成/血液 静脉血栓形成/遗传学 静脉血栓形成/病理生理学 玻连蛋白/缺乏 玻连蛋白/遗传学 玻连蛋白/生理学 动物 男(雄)性 小鼠 

摘      要：Occlusive thrombosis depends on the net balance between platelets, coagulation, and fibrinolytic factors. Epidemiologic information suggests that plasminogen activator inhibitor-1 (PAI-1), a central regulator of the fibrinolytic system, plays an important role in determining the overall risk for clinically significant vascular thrombosis. Vitronectin (VN), an abundant plasma and matrix glycoprotein, binds PAI-1 and stabilizes its active conformation. This study assessed the role of PAI-1 and VN expression in the formation of occlusive vascular thrombosis following arterial or venous injury. The common carotid arteries of 17 wild-type (WT) mice and 8 mice deficient in PAI-1 were injured photochemically while blood flow was continuously monitored. WT mice developed occlusive thrombi at 52.0 +/- 3.8 minutes (mean +/- SEM) following injury;mice deficient in PAI-1 developed occlusive thrombosis at 127 +/- 15 minutes (P .0001). Mice deficient in VN (n = 12) developed vascular occlusion 77 +/- 11 minutes after injury, intermediate between the values observed for WT mice (P .03) and mice deficient in PAI-1 (P .01). PAI-1 and VN also affected the time to occlusion after injury to the jugular vein. Three WT mice developed occlusive venous thrombosis an average of 39.7 +/- 1 minutes following the onset of injury, whereas the jugular veins of 4 mice deficient in PAI-1 and 4 deficient in VN occluded 56.7 +/- 5 and 58.7 +/- 2 minutes, respectively, following injury (P .04 and P .01 compared to WT mice). These results suggest that endogenous fibrinolysis acid its regulation by PAI-1 and VN have important roles in the development of occlusive vascular thrombosis after vascular injury.