Drug Discovery Research Center, Southwest Medical University, Luzhou, Sichuan, China.
Department of Medicine, University of Missouri School of Medicine, Columbia, MO.
J Am Heart Assoc. 2017 Jul 3;6(7):e006345. doi: 10.1161/JAHA.117.006345.
Coagulation factor V (FV) plays a key role in hemostasis, is present in plasma and platelets, and has both pro- and anticoagulant properties; however, the contribution of platelet-derived FV to arterial thrombosis remains undetermined.
Using transgenic mice with various levels of FV gene expression that was restricted to the plasma or platelets, the roles of platelet FV were evaluated in the regulation of arterial thrombosis and platelet activation. Mice with higher levels of platelet FV exhibited faster thrombotic occlusion of the carotid artery after injury compared with mice with lower platelet FV levels. Infusion of platelets with higher levels of FV into transgenic mice with undetectable levels of platelet FV reduced the time to carotid artery occlusion. In contrast, infusion of purified recombinant plasma FV into mice with undetectable platelet FV levels failed to reduce the carotid occlusion times following injury. Evaluation of isolated platelets revealed that platelet-derived FV was critical for the regulation of platelet activation. These effects were associated with an increased level of expression of P-selectin and increased cGMP in platelets.
We established that platelet-derived FV is a critical mediator of arterial thrombosis that involves platelet activation.
凝血因子 V（FV）在止血中起着关键作用，存在于血浆和血小板中，具有促凝和抗凝特性；然而，血小板衍生的 FV 对动脉血栓形成的贡献仍未确定。
使用转基因小鼠，其 FV 基因表达水平受到限制，仅限于血浆或血小板，评估了血小板 FV 在调节动脉血栓形成和血小板激活中的作用。与血小板 FV 水平较低的小鼠相比，血小板 FV 水平较高的小鼠在损伤后颈动脉血栓形成的闭塞更快。将 FV 水平较高的血小板输注到血小板 FV 水平检测不到的转基因小鼠中，可缩短颈动脉闭塞时间。相比之下，将纯化的重组血浆 FV 输注到血小板 FV 水平检测不到的小鼠中，不能减少损伤后颈动脉闭塞时间。对分离的血小板进行评估发现，血小板衍生的 FV 对血小板激活的调节至关重要。这些作用与 P-选择素表达水平的增加和血小板中环鸟苷酸（cGMP）的增加有关。
我们确定了血小板衍生的 FV 是涉及血小板激活的动脉血栓形成的关键介质。
