Shear stress and the role of high molecular weight von Willebrand factor multimers in thrombus formation
Shear stress and the role of high molecular weight von Willebrand factor multimers in thrombus formation
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DOI：
10.1097/01.mbc.0000167657.85143.ad
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发表时间：
2005-04-01
影响因子：
1.1
通讯作者：
Dong, JF
中科院分区：
文献类型：
--
作者：
López, JA;Dong, JF
高分子量血管性血友病因子（VWF）多聚体在快速血流导致的高剪切应力条件下血小板血栓的形成中起重要作用。使用内皮细胞系统进行的实验室研究表明，超大型VWF多聚体（ULVWF）附着在组胺刺激的内皮细胞表面，并形成血小板粘附的大型线状结构。血小板粘附是通过血小板Gplb-IX-V复合物的糖蛋白（Gp） Ib α亚基与vvwf的A1结构域的相互作用介导的。这些血小板- ulvwf链通过添加正常人血浆或纯化的血浆金属蛋白酶ADAMTS-13（一种具有血小板反应蛋白I型基元结构域的崩解素和金属蛋白酶）而迅速断裂。先天性或获得性血栓性血小板减少性紫癜（TTP）患者的血浆以及正常血浆与获得性TTP患者血浆的混合物中缺乏切割活性。VWF与p -选择素的相互作用至少部分地解释了VWF串附着在内皮细胞上的原因。流动血液中的p -选择素将ULVWF链系在内皮表面，从而增加ULVWF多聚体的拉伸应力，可能暴露出VWF A2结构域的裂解位点，从而促进ADAMTS-13对多聚体的降解。这些研究对出血和血栓性疾病有重要意义，包括血管性血友病和TTP。(c) 2005年Lippincott Williams & Wilkins。
High molecular weight von Willebrand factor (VWF) multimers have an important role in the formation of platelet thrombi under conditions of high shear stress resulting from rapid blood flow. Laboratory-studies conducted using an endothelial cell system-have shown that ultra-large VWF multimers (ULVWF) attach to the surface of histamine-stimulated endothelial cells and form large string-like structures to which platelets adhere. Platelet attachment is mediated through the interaction of the glycoprotein (Gp) Ib alpha subunit of the platelet Gplb-IX-V complex with the A1 domain of VWF These platelet-ULVWF strings are rapidly cleaved by the addition of normal human plasma or the purified plasma metalloprotease ADAMTS-13 (a disintegrin and metalloprotease with thrombospondin type I motifs domains). Cleaving activity is absent from the plasma of patients with the congenital or acquired forms of thrombotic thrombocytopenic purpura (TTP) and from mixtures of normal plasma with plasma from patients with acquired TTP. The interaction of VWF with P-selectin is at least partially responsible for the attachment of the VWF strings to the endothelium. Increased tensile stress on ULVWF multimers resulting from the tethering of ULVWF strings to the endothelial surface by P-selectin in flowing blood may expose the cleavage site on the A2 domain of VWF, facilitating multimer degradation by ADAMTS-13. These studies have important implications in bleeding and thrombotic disorders, including von Willebrand disease and TTP. (c) 2005 Lippincott Williams & Wilkins.