Cardiology Division, Department of Internal Medicine, Jeju National University Hospital, Jeju, Korea.
Korean Circ J. 2012 May;42(5):295-301. doi: 10.4070/kcj.2012.42.5.295. Epub 2012 May 24.
Platelet aggregation is not only an essential part of hemostasis, but also initiates acute coronary syndrome or ischemic stroke. The precise understanding of the activation mechanism of platelet aggregation is fundamental for the development of more effective agents against platelet aggregation. Adenosine diphosphate, thrombin, and thromboxane A(2) activate platelet integrin αIIbβ3 through G protein-coupled receptors. G protein-mediated signaling pathways, which are initiated by G(q), G(12)/G(13) or G(i), include phospholipase C with calcium signaling, Rho signaling, protein kinase C and phosphatidylinositol 3-kinase. Rap1b, Ca(2+) and diacylglycerol-regulated guanine nucleotide exchange factor I, Rap1-GTP-interacting adaptor molecule, and Akt are important proteins involved in G protein-mediated activation of integrin αIIbβ3. Binding of talin-1 and kindlin-3 to cytoplasmic domains of β3-integrin triggers a conformational change in the extracellular domains that increases its affinity for ligands, such as fibrinogen or von Willebrand factor. Fibrinogens act as bridges between adjacent platelets to generate a platelet aggregate.
血小板聚集不仅是止血的重要组成部分，也是急性冠状动脉综合征或缺血性卒中的起始步骤。精确理解血小板聚集的激活机制是开发更有效的抗血小板聚集药物的基础。二磷酸腺苷、凝血酶和血栓烷 A2 通过 G 蛋白偶联受体激活血小板整合素 αIIbβ3。由 G(q)、G(12)/G(13)或 G(i)启动的 G 蛋白介导的信号通路包括钙信号转导的磷脂酶 C、Rho 信号转导、蛋白激酶 C 和磷脂酰肌醇 3-激酶。Rap1b、Ca2+和二酰基甘油调节的鸟嘌呤核苷酸交换因子 I、Rap1-GTP 相互作用衔接分子和 Akt 是参与 G 蛋白介导的整合素 αIIbβ3 激活的重要蛋白。连接蛋白-1 和伴肌动蛋白-3 与 β3 整合素胞质结构域的结合触发细胞外结构域的构象变化，增加其与纤维蛋白原或血管性血友病因子等配体的亲和力。纤维蛋白原在相邻血小板之间充当桥梁，形成血小板聚集物。
