Ruggeri Z M
Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037, USA.
Thromb Haemost. 1997 Jul;78(1):611-6.
The functions of platelets depend on their ability to interest with surface exposed at sites of tissue damage and then with one another after activation, thus aggregating into thrombi. This complex process, normally beneficial to arrest bleeding during hemostasis, may become a cause of catastrophic disease when it leads to thrombotic occlusion of atherosclerotic vessels curtailing arterial blood flow to vital organs. Fluid dynamic conditions modulate all aspects of platelet response to vascular injury. At higher levels of shear stress, encountered both in normal vessels during normal hemostasis or in pathological conditions of the vasculature during thrombosis, von Willebrand factor becomes the essential adhesive protein for both adhesion and aggregation. Two platelet membrane receptors, the glycoprotein complexes Ib-IX-V and IIb-IIIa (integrin alpha IIb beta 3), mediate the von Willebrand factor function in a coordinate and synergistic manner, each contributing unique biomechanical properties to support thrombus formation. The developing understanding of the structure and mechanism of action of the key adhesive domains of von Willebrand factor, as well as of their cognate cellular and extracellular binding sites, will provide solid pathophysiological foundation for the evaluation of novel anti-thrombotic strategies.
血小板的功能取决于它们与组织损伤部位暴露的表面相互作用的能力，以及激活后彼此之间的相互作用能力，从而聚集形成血栓。这个复杂的过程通常有助于在止血过程中阻止出血，但当它导致动脉粥样硬化血管的血栓性闭塞，减少流向重要器官的动脉血流时，可能会成为灾难性疾病的原因。流体动力学条件调节血小板对血管损伤反应的各个方面。在正常止血过程中正常血管内或血栓形成时血管系统的病理状态下遇到的较高剪切应力水平下，血管性血友病因子成为黏附与聚集的关键黏附蛋白。两种血小板膜受体，糖蛋白复合物Ib-IX-V和IIb-IIIa（整合素αIIbβ3），以协调和协同的方式介导血管性血友病因子的功能，各自为血栓形成提供独特的生物力学特性。对血管性血友病因子关键黏附结构域的结构和作用机制以及它们相应的细胞内和细胞外结合位点的深入理解，将为评估新型抗血栓策略提供坚实的病理生理学基础。
