High Shear Dependent vonWillebrand Factor Self-assembly Fostered by Platelet Interaction and Controlled by ADAMTS13
High Shear Dependent vonWillebrand Factor Self-assembly Fostered by Platelet Interaction and Controlled by ADAMTS13
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DOI：
10.1016/j.thromres.2014.03.024
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发表时间：
2014-06-01
影响因子：
7.5
通讯作者：
Reininger, Armin J.
中科院分区：
文献类型：
--
作者：
Kragh, Thorsten;Napoleone, Marina;Reininger, Armin J.
最近，在剪切速率超过20,000 s（-1）的血流条件下，活化诱导血小板聚集的范式被反驳。这些导致可逆的滚动血小板聚集，这是依赖于固定和可溶性血管性血友病因子的存在。材料和方法：体外实验采用直接荧光视频显微镜，在壁面平行和驻点流室中进行，剪切速率从20,000到50,000 s（-1）。将含有重组血管性血友病因子（rVWF）的洗过的血细胞悬液灌注于rVWF或胶原包被的表面。结果：我们首次通过rVWF的可视化显示，不仅胶体和聚合物，即血小板和VWF可以形成复合材料，而且VWF本身具有完全可逆的自组装能力。在胶原蛋白表面，血小板-VWF聚集体不滚动，但VWF网永久地与胶原纤维结合，并从流动中捕获和固定血小板。将剪切速率降低到20,000 s（-1）以下，这些沉积物不再溶解。与正常大小的rVWF相比，超大型多定时器的rVWF效果最好。ADAMTS13的存在将滚动骨料和血小板- vwf砾岩的形成限制在7-8分钟的时间窗口内。将壁面平行流改为驻点流，所需剪切速率阈值减半。结论：血流动力学可触发可逆性血管性血液病因子自组装和血小板- vwf堆积，ADAMTS13可将其调节至凝血所需的稳定时间范围，例如在血管损伤的情况下。(C) 2014 Elsevier Ltd.版权所有。
Introduction: The paradigm of activation induced platelet aggregation has recently been refuted under blood flow conditions with shear rates exceeding 20,000 s(-1). These lead to reversible rolling platelet aggregates, which were dependent on the presence of immobilized and soluble von Willebrand factor.Material and Methods: In vitro experiments using direct fluorescence video-microscopy were performed in wall parallel and stagnation point flow chambers with shear rates raised from 20,000 to 50,000 s(-1). Washed blood cell suspension containing recombinant von Willebrand factor (rVWF) was perfused over rVWF or collagen coated surfaces.Results: Here we show for the first time with the visualization of rVWF that not only colloid and polymer, i.e. platelets and VWF, form a composite, but that VWF itself is capable of entirely reversible self-assembly. On a collagen surface the platelet-VWF-conglomerates did not roll but VWF nets bound permanently to the collagen fibers and captured and immobilized platelets from the flow. Lowering the shear rate below the threshold of 20,000 s(-1) no longer dissolved these deposits. Ultralarge multimer containing rVWF was most effective compared to normal sized rVWF. The presence of ADAMTS13 limited rolling aggregate and platelet-VWF-conglomerate formation to a time window of 7-8 minutes. Changing wall parallel flow to stagnation point flow halved the required shear rate threshold.Conclusion: We conclude that flow dynamics can trigger reversible von Willebrand factor self-assembly and platelet-VWF-conglomerate accrual, which are regulated by ADAMTS13 to a time span needed by coagulation to stabilize it, e.g. in case of vessel injury. (C) 2014 Elsevier Ltd. All rights reserved.