Packham M A
Department of Biochemistry, University of Toronto, ON, Canada.
Can J Physiol Pharmacol. 1994 Mar;72(3):278-84. doi: 10.1139/y94-043.
Platelet aggregates, stabilized by fibrin, rapidly form hemostatic plugs when blood vessels are severed or arterial thrombi at sites of vessel injury, such as ruptured atherosclerotic plaques, or regions where blood flow is disturbed, such as at stenoses. These thrombi cause the thromboembolic complications of atherosclerosis: heart attacks, strokes, and peripheral vascular disease. Platelet adhesion to subendothelial components such as collagen activates signalling pathways that lead to thromboxane A2 formation and secretion of platelet granule contents, including ADP. Both these substances cause platelet aggregation, a process in which the integrin, glycoprotein IIb/IIIa, becomes a receptor for fibrinogen, which forms bridges between adjacent platelets. On the surface of stimulated platelets, coagulation is accelerated and thrombin is generated; it is a potent inducer of platelet aggregation and secretion and also causes fibrin to form around the aggregates, stabilizing them. There are receptors on the platelet surface for thrombin, thromboxane A2, collagen, ADP, platelet-activating factor, fibrinogen, von Willebrand factor, and other ligands. Agents that inhibit platelet aggregation and the signalling pathways that are activated by the various aggregating agents are under intensive investigation in many laboratories.
当血管被切断时，由纤维蛋白稳定的血小板聚集体迅速形成止血栓；在血管损伤部位，如破裂的动脉粥样硬化斑块处，或血流受到干扰的区域，如狭窄处，会形成动脉血栓。这些血栓会引发动脉粥样硬化的血栓栓塞并发症：心脏病发作、中风和外周血管疾病。血小板与诸如胶原蛋白等内皮下成分的黏附会激活信号通路，导致血栓素A2的形成以及包括ADP在内的血小板颗粒内容物的分泌。这两种物质都会引起血小板聚集，在这个过程中，整合素糖蛋白IIb/IIIa成为纤维蛋白原的受体，纤维蛋白原在相邻血小板之间形成桥梁。在受刺激的血小板表面，凝血加速并产生凝血酶；凝血酶是血小板聚集和分泌的强效诱导剂，还会使纤维蛋白在聚集体周围形成，使其稳定。血小板表面存在针对凝血酶、血栓素A2、胶原蛋白、ADP、血小板活化因子、纤维蛋白原、血管性血友病因子及其他配体的受体。许多实验室正在深入研究抑制血小板聚集以及由各种聚集剂激活的信号通路的药物。
