Factor XI as a Therapeutic Target.
Factor XI as a Therapeutic Target.
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DOI：
10.1161/atvbaha.116.306925
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发表时间：
2016-07
期刊：
影响因子：
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通讯作者：
Gruber A
中科院分区：
文献类型：
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作者：
Gailani D;Gruber A
XIa因子是一种血浆丝氨酸蛋白酶，主要通过IX因子的蛋白水解激活来促进凝血酶的产生。传统上被认为是凝血内在途径的一部分，现在有几条证据表明，XIa因子作为维生素k依赖性凝血酶生成机制和促炎钾likrein-kinin系统之间的接口，使两个系统相互影响。动物模型研究和人群流行病学调查结果支持XIa因子在血栓栓塞性疾病中的作用。这些数据，以及临床观察到缺乏因子XI （XIa因子的酶原）会导致相对轻微的出血性疾病，这表明靶向因子XI或XIa的药物可以在止血基本完好的情况下产生抗血栓作用。最近的一项试验比较了反义诱导的因子XI降低与标准剂量低分子量肝素作为预防膝关节置换术中静脉血栓形成的结果，在这些方面令人鼓舞。在这里，我们讨论因子XI的生物化学、生理学和病理学的最新发现，因为它们与血栓栓塞性疾病有关。
Factor XIa is a plasma serine protease that contributes to thrombin generation primarily through proteolytic activation of factor IX. Traditionally considered part of the intrinsic pathway of coagulation, several lines of evidence now suggest that factor XIa serves as an interface between the vitamin-K dependent thrombin generation mechanism and the pro-inflammatory kallikrein-kinin system, allowing the two systems to influence each other. Work with animal models and results from epidemiologic surveys of human populations support a role for factor XIa in thromboembolic disease. These data, and the clinical observation that deficiency of factor XI, the zymogen of factor XIa, produces a relatively mild bleeding disorder suggest that drugs targeting factor XI or XIa could produce an antithrombotic effect while leaving hemostasis largely intact. Results of a recent trial comparing antisense-induced factor XI reduction to standard dose low molecular weight heparin as prophylaxis for venous thrombosis during knee replacement are encouraging in these regards. Here we discuss recent findings on the biochemistry, physiology and pathology of factor XI as they relate to thromboembolic disease.