Serpins in thrombosis, hemostasis and fibrinolysis
Serpins in thrombosis, hemostasis and fibrinolysis
复制标题
DOI：
10.1111/j.1538-7836.2007.02516.x
复制
发表时间：
2007-07-01
影响因子：
10.4
通讯作者：
Church, F. C.
中科院分区：
文献类型：
--
作者：
Rau, J. C.;Beaulieu, L. M.;Church, F. C.
止血和纤维蛋白溶解是维持正常血流的生物学过程，是一系列复杂的级联酶反应的结果。参与这些过程的丝氨酸蛋白酶受反馈环、局部辅因子分子和丝氨酸蛋白酶抑制剂（丝氨酸蛋白酶抑制剂）的调节。凝血、蛋白C和纤维蛋白溶解途径所描述的止血和纤维蛋白溶解中蛋白水解和抑制反应之间的微妙平衡可能被破坏，导致血栓形成或异常出血的病理状况。医学利用蛇蛋白酶抑制剂的重要性，使用治疗方法来操纵蛇蛋白酶抑制剂-蛋白酶反应，以治疗和预防血栓形成和出血。因此，研究丝氨酸蛋白酶抑制剂、它们的辅因子以及它们的结构-功能关系对于开发用于选择性微调止血和纤溶的最先进药物是必要的。本文综述了在这些途径的调节中重要的丝氨酸蛋白酶抑制剂：抗凝血酶，肝素辅因子II，蛋白Z依赖性蛋白酶抑制剂，α（1）-蛋白酶抑制剂，蛋白C抑制剂，α（2）-抗纤溶酶和纤溶酶原激活物抑制剂-1。我们专注于生物学功能，重要的结构元素，其已知的非止血作用，与缺陷或功能障碍相关的病理学，以及特定丝氨酸蛋白酶抑制剂的治疗作用。
Hemostasis and fibrinolysis, the biological processes that maintain proper blood flow, are the consequence of a complex series of cascading enzymatic reactions. Serine proteases involved in these processes are regulated by feedback loops, local cofactor molecules, and serine protease inhibitors (serpins). The delicate balance between proteolytic and inhibitory reactions in hemostasis and fibrinolysis, described by the coagulation, protein C and fibrinolytic pathways, can be disrupted, resulting in the pathological conditions of thrombosis or abnormal bleeding. Medicine capitalizes on the importance of serpins, using therapeutics to manipulate the serpin-protease reactions for the treatment and prevention of thrombosis and hemorrhage. Therefore, investigation of serpins, their cofactors, and their structure-function relationships is imperative for the development of state-of-the-art pharmaceuticals for the selective fine-tuning of hemostasis and fibrinolysis. This review describes key serpins important in the regulation of these pathways: antithrombin, heparin cofactor II, protein Z-dependent protease inhibitor, alpha(1)-protease inhibitor, protein C inhibitor, alpha(2)-antiplasmin and plasminogen activator inhibitor-1. We focus on the biological function, the important structural elements, their known non-hemostatic roles, the pathologies related to deficiencies or dysfunction, and the therapeutic roles of specific serpins.