A shear gradient-dependent platelet aggregation mechanism drives thrombus formation
A shear gradient-dependent platelet aggregation mechanism drives thrombus formation
复制标题
DOI：
10.1038/nm.1955
复制
发表时间：
2009-06-01
期刊：
影响因子：
82.9
通讯作者：
Jackson, Shaun P.
中科院分区：
文献类型：
--
作者：
Nesbitt, Warwick S.;Westein, Erik;Jackson, Shaun P.
血管损伤部位的血小板聚集对于止血和动脉血栓形成是必不可少的。长期以来，人们一直认为血小板聚集和血栓生长是由血管损伤部位产生的可溶性激动剂引发的。通过使用高分辨率活体成像技术和流体动力学分析，我们表明，血小板聚集主要是由血流参数（流变学）的变化，可溶性激动剂具有次要作用，稳定形成的聚集体。我们发现，在血管损伤的反应中，血栓最初是通过盘状血小板聚集体的逐渐稳定而形成的。血流动力学分析表明，盘状血小板优先粘附在低剪切区形成血栓的下游面，与稳定的聚集体依赖于膜系链的动态重组。这些发现提供了对血流参数紊乱的促血栓形成作用的深入了解，并提出了对驱动血小板聚集和血栓生长的机制的根本性重新解释。
Platelet aggregation at sites of vascular injury is essential for hemostasis and arterial thrombosis. It has long been assumed that platelet aggregation and thrombus growth are initiated by soluble agonists generated at sites of vascular injury. By using high-resolution intravital imaging techniques and hydrodynamic analyses, we show that platelet aggregation is primarily driven by changes in blood flow parameters (rheology), with soluble agonists having a secondary role, stabilizing formed aggregates. We find that in response to vascular injury, thrombi initially develop through the progressive stabilization of discoid platelet aggregates. Analysis of blood flow dynamics revealed that discoid platelets preferentially adhere in low-shear zones at the downstream face of forming thrombi, with stabilization of aggregates dependent on the dynamic restructuring of membrane tethers. These findings provide insight into the prothrombotic effects of disturbed blood flow parameters and suggest a fundamental reinterpretation of the mechanisms driving platelet aggregation and thrombus growth.