Functional imaging of shear-dependent activity of ADAMTS13 in regulating mural thrombus growth under whole blood flow conditions
Functional imaging of shear-dependent activity of ADAMTS13 in regulating mural thrombus growth under whole blood flow conditions
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DOI：
10.1182/blood-2007-09-110700
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发表时间：
2008-02-01
期刊：
影响因子：
20.3
通讯作者：
Yoshioka, Akira
中科院分区：
文献类型：
--
作者：
Shida, Yasuaki;Nishio, Kenji;Yoshioka, Akira
假定金属蛋白酶ADAMTS13通过减少血管性血友病因子（VWF）多聚体大小（其直接代表该因子的血栓形成活性）来调节适于体内正常止血的VWF功能水平。使用体外灌注室系统，我们研究了ADAMTS13在全血流条件下胶原表面血小板血栓形成过程中的作用机制。使用功能阻断抗ADAMTS13抗体进行的抑制研究，结合使用特异性反映ADAMTS13 VWF切割活性的抗VWF单克隆抗体进行的血栓免疫染色，为ADAMTS13的剪切速率依赖性作用提供了直观证据，该作用直接限制了正在进行的血栓生成过程部位的血栓生长。我们的研究结果确定了一个精致的具体的监管机制，防止动脉闭塞在高剪切率条件下，在壁血栓形成。
The metalloprotease ADAMTS13 is assumed to regulate the functional levels of von Willebrand factor (VWF) appropriate for normal hemostasis in vivo by reducing VWF multimer size, which directly represents the thrombogenic activity of this factor. Using an in vitro perfusion chamber system, we studied the mechanisms of ADAMTS13 action during platelet thrombus formation on a collagen surface under whole blood flow conditions. Inhibition studies with a function-blocking anti-ADAMTS13 antibody, combined with immunostaining of thrombi with an anti-VWF monoclonal antibody that specifically reflects the VWF-cleaving activity of ADAMTS13, provided visual evidence for a shear rate-dependent action of ADAMTS13 that limits thrombus growth directly at the site of the ongoing thrombus generation process. Our results identify an exquisitely specific regulatory mechanism that prevents arterial occlusion under high shear rate conditions during mural thrombogenesis.