Miyazaki Y, Nomura S, Miyake T, Kagawa H, Kitada C, Taniguchi H, Komiyama Y, Fujimura Y, Ikeda Y, Fukuhara S
First Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
Blood. 1996 Nov 1;88(9):3456-64.
Previous studies have demonstrated that a high level of shear stress can produce platelet aggregation without the addition of any agonist. We investigated whether high shear stress could cause both platelet aggregation and shedding of microparticles from the platelet plasma membrane. A coneplate viscometer was used to apply shear stress and microparticle formation was measured by flow cytometry. It was found that microparticle formation increased as the duration of shear stress increased. Both microparticles and the remnant platelets showed the exposure of procoagulant activity on their surfaces. Investigation of the mechanisms involved in shear-dependent microparticle generation showed that binding of von Willebrand factor (vWF) to platelet glycoprotein lb, influx of extracellular calcium, and activation of platelet calpain were required to generate microparticles under high shear stress conditions. Activation of protein kinase C (PKC) promoted shear-dependent microparticle formation. Epinephrine did not influence microparticle formation, although it enhanced platelet aggregation by high shear stress. These findings suggest the possibility that local generation of microparticles in atherosclerotic arteries, the site that pathologically high shear stress could occur, may contribute to arterial thrombosis by providing and expanding a catalytic surface for the coagulation cascade.
先前的研究表明，在不添加任何激动剂的情况下，高水平的剪切应力可导致血小板聚集。我们研究了高剪切应力是否会导致血小板聚集以及血小板质膜微粒的脱落。使用锥板粘度计施加剪切应力，并通过流式细胞术测量微粒形成。结果发现，微粒形成随着剪切应力持续时间的增加而增加。微粒和残余血小板在其表面均显示促凝活性的暴露。对剪切依赖性微粒生成所涉及机制的研究表明，在高剪切应力条件下生成微粒需要血管性血友病因子（vWF）与血小板糖蛋白lb结合、细胞外钙内流以及血小板钙蛋白酶激活。蛋白激酶C（PKC）的激活促进了剪切依赖性微粒形成。肾上腺素虽通过高剪切应力增强血小板聚集，但不影响微粒形成。这些发现提示，在动脉粥样硬化动脉（可能出现病理性高剪切应力的部位）局部生成微粒，可能通过为凝血级联反应提供并扩展催化表面而促进动脉血栓形成。
