Platelet aggregation pathway.
Platelet aggregation pathway.
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DOI：
10.1097/fpc.0b013e3283406323
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发表时间：
2011-08
影响因子：
2.6
通讯作者：
Altman RB
中科院分区：
文献类型：
--
作者：
Sangkuhl K;Shuldiner AR;Klein TE;Altman RB
正常情况下，完整的血管中不会发生血小板活化和凝血。血管壁损伤后，通过血小板与内皮下胶原蛋白[1，2]的黏附，启动了血小板堵塞的形成。在高切动脉血中，血小板首先通过与胶原结合的von Willebrand因子相互作用而减慢血流速度，然后通过其糖蛋白(GP)受体复合体直接与胶原结合而停止[2，3]。血小板上的这些胶原受体在与胶原结合后被激活，从而激活了磷脂酶C介导的级联反应(图1)[1-3]。这导致了从致密的小管系统中动员钙[4，5]。细胞内钙的增加与形态变化所需的几种激酶的激活、促凝血剂表面的呈现、血小板颗粒内容物的分泌、GP的激活和磷脂酶A2的激活(见图1)[2，5-7]有关。促凝血剂表面的存在导致不同凝血因子在激活的血小板表面共存，从而触发一系列酶原转换，导致活性凝血酶从凝血酶原[8]中释放出来。二磷酸腺苷(ADP)、三磷酸腺苷和5-羟色胺从致密的血小板颗粒中释放出来。激活的磷脂酶A2酶通过在其sn-2位置裂解脂肪酸，特别是磷脂酰胆碱和磷脂酰乙醇胺来释放花生四烯酸(AA)[9-11]。AA是血栓素A2(TBXA2)合成的前体。在血小板的第一步中，前列腺素(PG)-内源性过氧化物合成酶1(PTGS1；也称为环氧合酶1)催化AA转化为环状内源性过氧化物PG G2和H2[9]。在血小板中，PGG2和PGH2主要被TBXA合酶转化为TBXA2[9]。阿司匹林的作用机制是抑制PTGS1，从而阻止PGs的产生，特别是在血小板中，抑制TBXA2的产生[10-12]。在体外血小板聚集试验中，阿司匹林主要通过直接途径影响AA刺激的血小板聚集，也通过间接途径影响胶原刺激的血小板聚集。回顾
Platelet activation and coagulation normally do not occur in an intact blood vessel. After blood vessel wall injury, platelet plug formation is initiated by the adherence of the platelets to subendothelial collagen [1, 2]. In high shear arterial blood, platelets are first slowed down from their blood flow velocity by interacting with the collagenbound von Willebrand factor and are subsequently stopped by binding directly to the collagen by their glycoprotein (GP) receptor complex [2, 3]. The activation of these collagen receptors on platelets after their binding to the collagen activates phospholipase C-mediated cascades (Fig. 1)[1–3]. This results in the mobilization of calcium from the dense tubular system [4, 5]. An increase in intracellular calcium is associated with the activation of several kinases necessary for morphologic change, the presentation of the procoagulant surface, the secretion of platelet granular content, the activation of GPs, and the activation of phospholipase A2 (see Fig. 1)[2, 5–7]. The presentation of the procoagulant surface results in the colocalization of different coagulation factors on the surface of the activated platelet, which triggers a series of zymogen conversions, resulting in the release of active thrombin from prothrombin [8]. Adenosine diphosphate (ADP), adenosine triphosphate, and serotonin are released from the dense platelet granule. Activated phospholipase A2 enzymes release arachidonic acid (AA) by the cleaving of fatty acids, especially phosphatidylcholine and phosphatidylethanolamine, at their sn-2 position [9–11]. AA is a precursor for thromboxane A2 (TBXA2) synthesis. In the first step in platelets, prostaglandin (PG)-endoperoxide synthase 1 (PTGS1; also known as cyclooxygenase 1) catalyzes the transformation of AA into cyclic endoperoxide PG G2 and H2 [9]. In platelets, PGG2 and PGH2 are then mainly converted by TBXA synthase into TBXA2 [9].The mechanism of action of aspirin is the inhibition of PTGS1, thereby preventing the production of PGs and, particularly in platelets, inhibiting TBXA2 production [10–12]. In ex vivo platelet aggregation testing, aspirin affects predominantly AA-stimulated platelet aggregation through a direct pathway, and also collagen-stimulated platelet aggregation through indirect pathways. A review