The role of the platelet in the pathogenesis of atherothrombosis.
The role of the platelet in the pathogenesis of atherothrombosis.
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DOI：
10.2165/00129784-200505060-00007
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发表时间：
2005-01-01
期刊：
影响因子：
--
通讯作者：
Moliterno, David J
中科院分区：
文献类型：
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作者：
Steinhubl, Steven R;Moliterno, David J
血小板在动脉粥样硬化引起的血管内皮破坏部位的粘附、活化和聚集是动脉血栓形成的关键事件。血小板栓系和粘附于动脉壁，特别是在高剪切力下，是通过暴露的内皮下血小板膜受体（整合素）和配体（最显著的是胶原蛋白和血管性血友病因子（vWF））之间的多种高亲和力相互作用实现的。血小板与胶原蛋白的粘附既通过血小板糖蛋白（GP）Ib-V-IX受体与循环vWF（其与暴露的胶原蛋白结合）的结合间接发生，也通过与血小板受体GP VI和GP Ia/IIb的相互作用直接发生。由暴露的胶原蛋白和局部产生的可溶性血小板激动剂（主要是凝血酶、ADP和血栓烷A2）引发的血小板活化为血小板衍生生长因子、粘附分子和凝血因子的释放、相邻血小板的活化和血小板α（IIb）β 3整联蛋白（GP IIb/IIIa受体）的构象变化提供刺激。主要由活化的血小板GP IIb/IIIa受体及其配体、纤维蛋白原和vWF之间的相互作用介导的血小板聚集导致富血小板血栓的形成。目前可用的抗血小板药物（阿司匹林[乙酰水杨酸]、双嘧达莫、氯吡格雷、噻氯匹定、阿昔单抗、依替巴肽、替罗非班）作用于特定靶点，以抑制血小板活化和聚集。阐明血小板血栓形成的多种机制为选择性抑制与动脉粥样硬化血栓形成的病理生理学最相关的途径提供了机会。
Platelet adhesion, activation, and aggregation at sites of vascular endothelial disruption caused by atherosclerosis are key events in arterial thrombus formation. Platelet tethering and adhesion to the arterial wall, particularly under high shear forces, are achieved through multiple high-affinity interactions between platelet membrane receptors (integrins) and ligands within the exposed subendothelium, most notably collagen and von Willebrand factor (vWF). Platelet adhesion to collagen occurs both indirectly, via binding of the platelet glycoprotein (GP) Ib-V-IX receptor to circulating vWF, which binds to exposed collagen, and directly, via interaction with the platelet receptors GP VI and GP Ia/IIb. Platelet activation, initiated by exposed collagen and locally generated soluble platelet agonists (primarily thrombin, ADP, and thromboxane A2), provides the stimulus for the release of platelet-derived growth factors, adhesion molecules and coagulation factors, activation of adjacent platelets, and conformational changes in the platelet alpha(IIb)beta3 integrin (GP IIb/IIIa receptor). Platelet aggregation, mediated primarily by interaction between the activated platelet GP IIb/IIIa receptor and its ligands, fibrinogen and vWF, results in the formation of a platelet-rich thrombus. Currently available antiplatelet drugs (aspirin [acetylsalicylic acid], dipyridamole, clopidogrel, ticlopidine, abciximab, eptifibatide, tirofiban) act on specific targets to inhibit platelet activation and aggregation. Elucidation of the multiple mechanisms involved in platelet thrombus formation provides opportunities for selectively inhibiting the pathways most relevant to the pathophysiology of atherothrombosis.