Elongational Flow Induces the Unfolding of von Willebrand Factor at Physiological Flow Rates
Elongational Flow Induces the Unfolding of von Willebrand Factor at Physiological Flow Rates
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DOI：
10.1016/j.bpj.2010.01.032
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发表时间：
2010-05-05
影响因子：
3.4
通讯作者：
Alexander-Katz, Alfredo
中科院分区：
文献类型：
--
作者：
Sing, Charles E.;Alexander-Katz, Alfredo
血管性血友病因子（vWF）是人体内最大的多聚体蛋白之一，其解折叠已被证明是血液凝固过程中的关键步骤。在这里，我们表明，伸长流，出现在血管收缩或狭窄，是vWF的主要激活机制，并展开的多聚体蛋白的流速是两个数量级以下的那些对应于纯剪切。本文提出的研究结果补充了目前从分子到生理水平对血液凝固的理解，并为凝血异常（如Heyde综合征和狭窄）之间的联系提供了新的物理见解。这些发现也代表了vWF功能和激活的新范式。
The unfolding of von Willebrand Factor (vWF), one of the largest multimeric proteins in our body, has been shown to be a crucial step in the process of blood clotting. Here we show that elongational flows, which appear during vasoconstriction or stenosis, are the primary activation mechanisms of vWF, and unfold the multimeric protein at flow rates that are two orders-of-magnitude below those corresponding to pure shear. The findings presented here complement the current understanding of blood clotting from the molecular to the physiological level, and provide new physical insights into the connection between clotting anomalies, such as Heyde's syndrome and stenosis. These findings also represent a new paradigm in the function and activation of vWF.