Activation-independent platelet adhesion and aggregation under elevated shear stress
Activation-independent platelet adhesion and aggregation under elevated shear stress
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DOI：
10.1182/blood-2006-04-011551
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发表时间：
2006-09-15
期刊：
影响因子：
20.3
通讯作者：
Reininger, Armin J.
中科院分区：
文献类型：
--
作者：
Ruggeri, Zaverio M.;Orje, Jennifer N.;Reininger, Armin J.
血小板聚集，这有助于止血，也血栓性疾病，被认为是信号诱导的激活后启动。我们发现，这种模式并不适用于与狭窄冠状动脉中存在的血流条件相比。当存在可溶性血管性血友病因子（vonWillebrand factor，VWF）且剪切速率超过10 000 s（-1）（剪切应力= 400 dyn/cm（2））时，血小板与固定化VWF相互作用，不依赖于活化而聚集。高于此阈值，活性All结构域暴露于可溶性VWF多聚体中，并可结合糖蛋白Ib α，促进额外的血小板募集。由此形成的聚集体是不稳定的，直到剪切速率接近20 000 s（-1）（剪切应力= 800 dyn/cm.（2）译注。在此阈值以上，在表面固定和膜结合的VWF的界面处的粘附血小板被拉伸成细长的结构，并成为可以在表面上持续数分钟的聚集体的核心。当存在分离的二聚体All结构域而不是天然VWF多聚体时，不需要高于阈值水平的剪切应力就发生活化非依赖性血小板聚集，但聚集体从未牢固地附着于表面，并且当剪切速率超过6000 s（-1）时逐渐解聚。流体动力对血小板和VWF的调节是激活非依赖性聚集的机制，可能支持血栓性动脉闭塞。
Platelet aggregation, which contributes to bleeding arrest and also to thrombovascular disorders, is thought to initiate after signaling-induced activation. We found that this paradigm does not apply under blood flow conditions comparable to those existing in stenotic coronary arteries. Platelets interacting with immobilized von Willebrand factor (VWF) aggregate independently of activation when soluble VWF is present and the shear rate exceeds 10 000 s(-1) (shear stress = 400 dyn/cm(2)). Above this threshold, active All domains become exposed in soluble VWF multimers and can bind to glycoprotein Ib alpha, promoting additional platelet recruitment. Aggregates thus formed are unstable until the shear rate approaches 20 000 s(-1) (shear stress = 800 dyn/cm.(2)). Above this threshold, adherent platelets at the interface of surface-immobilized and membrane-bound VWF are stretched into elongated structures and become the core of aggregates that can persist on the surface for minutes. When isolated dimeric All domain is present instead of native VWF multimers, activation-independent platelet aggregation occurs without requiring shear stress above a threshold level, but aggregates never become firmly attached to the surface and progressively disaggregate as shear rate exceeds 6000 s(-1). Platelet and VWF modulation by hydrodynamic force is a mechanism for activation-independent aggregation that may support thrombotic arterial occlusion.