In vivo roles of factor XII
In vivo roles of factor XII
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DOI：
10.1182/blood-2012-07-292094
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发表时间：
2012-11-22
期刊：
影响因子：
20.3
通讯作者：
Maas, Coen
中科院分区：
文献类型：
--
作者：
Renne, Thomas;Schmaier, Alvin H.;Maas, Coen
凝血因子XII(FXII，Hageman因子，EC=3.4.21.38)是丝氨酸蛋白酶XIIa因子(FXIIa)的酶原。FXII通过与带电表面“接触”而自动激活而转化为FXIIa。FXIIa在体外对纤维蛋白的形成至关重要，但该酶缺乏与出血过多无关。几十年来，FXII被认为在体内没有凝血功能。我们实验室建立了第一个小鼠FXII基因敲除模型。与人类同行一致，FXII-/-小鼠具有正常的止血能力。然而，FXII-/-小鼠体内的血栓形成在很大程度上是有缺陷的，这些动物受到保护，免受实验性脑缺血和肺栓塞的影响。这种小鼠模型引起了人们对FXII的新兴趣，因为它提高了安全抗凝的可能性，这种抗凝作用针对血栓而不影响止血。我们最近发现，血小板聚磷酸(一种无机聚合物)和肥大细胞肝素是体内FXII激活剂，与超敏反应中血栓形成和水肿的启动有关。FXII独立于其蛋白水解酶活性，发挥促有丝分裂活性，与血管生成有关。本文对FXII的体内功能进行综述，重点介绍其在血栓形成和血管生物学中的作用。(血。2012；120(22)：4296-4303)
Coagulation factor XII (FXII, Hageman factor, EC = 3.4.21.38) is the zymogen of the serine protease, factor XIIa (FXIIa). FXII is converted to FXIIa through autoactivation induced by "contact" to charged surfaces. FXIIa is of crucial importance for fibrin formation in vitro, but deficiency in the protease is not associated with excessive bleeding. For decades, FXII was considered to have no function for coagulation in vivo. Our laboratory developed the first murine knockout model of FXII. Consistent with their human counterparts, FXII-/- mice have a normal hemostatic capacity. However, thrombus formation in FXII-/- mice is largely defective, and the animals are protected from experimental cerebral ischemia and pulmonary embolism. This murine model has created new interest in FXII because it raises the possibility for safe anticoagulation, which targets thrombosis without influence on hemostasis. We recently have identified platelet polyphosphate (an inorganic polymer) and mast cell heparin as in vivo FXII activators with implications on the initiation of thrombosis and edema during hypersensitivity reactions. Independent of its protease activity, FXII exerts mitogenic activity with implications for angiogenesis. The goal of this review is to summarize the in vivo functions of FXII, with special focus to its functions in thrombosis and vascular biology. (Blood. 2012;120(22):4296-4303)