Signaling events underlying thrombus formation
Signaling events underlying thrombus formation
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DOI：
10.1046/j.1538-7836.2003.00267.x
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发表时间：
2003-07-01
影响因子：
10.4
通讯作者：
Kulkarni, S
中科院分区：
文献类型：
--
作者：
Jackson, SP;Nesbitt, WS;Kulkarni, S
最近的体内研究强调了血小板血栓生长的动态性和复杂性，以及在此过程中需要多种粘附受体-配体相互作用。特别是，血管性血友病因子（VWF）在高剪切条件下促进原发性粘附和聚集的重要性现已得到充分证实。通常，血小板在血管壁损伤部位粘附和聚集的效率取决于各种粘附性和可溶性激动剂受体的协同作用，其中每种单独受体的贡献取决于主要的血流条件。在这篇综述中，我们将讨论在高剪切下调节血小板血栓形成的主要血小板粘附相互作用，特别关注VWF（GPIb和整合素α（IIb）β（3））和胶原蛋白受体（GPVI和整合素α（2）β（1））。我们还将讨论这些受体诱导血小板活化的信号传导机制，特别强调胞浆钙流在调节血小板粘附动力学中的作用。可溶性激动剂在促进血栓生长中的作用将被强调，并将讨论一个模型来解释有效的血小板聚集的粘合剂和可溶性刺激的协同需求。
Recent in vivo studies have highlighted the dynamic and complex nature of platelet thrombus growth and the requirement for multiple adhesive receptor-ligand interactions in this process. In particular, the importance of von Willebrand factor (VWF) in promoting both primary adhesion and aggregation under high shear conditions is now well established. In general, the efficiency with which platelets adhere and aggregate at sites of vessel wall injury is dependent on the synergistic action of various adhesive and soluble agonist receptors, with the contribution of each of the individual receptors dependent on the prevailing blood flow conditions. In this review, we will discuss the major platelet adhesive interactions regulating platelet thrombus formation under high shear, with specific focus on the VWF (GPIb and integrin alpha(IIb)beta(3)) and collagen receptors (GPVI and integrin alpha(2)beta(1)). We will also discuss the signaling mechanisms utilized by these receptors to induce platelet activation with specific emphasis on the role of cytosolic calcium flux in regulating platelet adhesion dynamics. The role of soluble agonists in promoting thrombus growth will be highlighted and a model to explain the synergistic requirement for adhesive and soluble stimuli for efficient platelet aggregation will be discussed.