THE ROLE OF VONWILLEBRAND-FACTOR AND FIBRINOGEN IN PLATELET-AGGREGATION UNDER VARYING SHEAR-STRESS
THE ROLE OF VONWILLEBRAND-FACTOR AND FIBRINOGEN IN PLATELET-AGGREGATION UNDER VARYING SHEAR-STRESS
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DOI：
10.1172/jci115124
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发表时间：
1991-04-01
影响因子：
15.9
通讯作者：
RUGGERI, ZM
中科院分区：
文献类型：
--
作者：
IKEDA, Y;HANDA, M;RUGGERI, ZM
在没有外源激动剂的情况下，血小板暴露于剪切应力导致聚集。我们现在已经发现，不同的粘附蛋白和血小板膜糖蛋白参与聚集取决于剪切应力条件和二价阳离子在介质中的浓度。当用柠檬酸三钠作为抗凝剂采集血液时，会导致外部离子钙（[Ca 2 +]0）水平降低，在低剪切力（12 dyn/cm 2）下可诱导血小板聚集，并通过纤维蛋白原与糖蛋白IIb-IIIa复合物结合介导。在这些条件下形成的聚集体是不稳定的，并且当剪切力增加到68达因/厘米2时，导致解聚。相比之下，用水蛭素作为抗凝剂采集的血液中的血小板（其中[Ca 2 +]0在正常血浆水平内）不会发生低剪切诱导的聚集;然而，在暴露于80 dyn/cm 2以上的剪切力后，观察到聚集，但仅当存在血管性血友病因子并可与其血小板结合位点（糖蛋白Ib-IX和糖蛋白IIb-IIIa）相互作用时。纤维蛋白原不参与高剪切诱导的聚集，事实上，高剪切诱导的聚集在严重无纤维蛋白原血症患者中正常发生。因此，在没有外源性激动剂的情况下，血管性血友病因子可以在模拟部分闭塞动脉的血液流变学情况的实验条件下介导血小板聚集。这种血小板聚集途径仅涉及一个粘附配体和两个膜粘附受体，可能在血栓形成中起相关作用。
Exposure of platelets to shear stress leads to aggregation in the absence of exogenous agonists. We have now found that different adhesive proteins and platelet membrane glycoproteins are involved in aggregation depending on the shear stress conditions and the concentration of divalent cations in the medium. When blood is collected with trisodium citrate as anticoagulant, which causes a decrease in the levels of external ionized calcium ([Ca2+]0), platelet aggregation can be induced under low shear force (12 dyn/cm2) and is mediated by fibrinogen binding to the glycoprotein IIb-IIIa complex. Aggregates formed under these conditions are not stable, and when shear force is increased to 68 dyn/cm2, disaggregation results. By contrast, platelets from blood collected with hirudin as anticoagulant, wherein [Ca2+]0 is within normal plasma levels, do not undergo low shear-induced aggregation; however, after exposure to a shear force above 80 dyn/cm2, aggregation is observed but only when von Willebrand factor is present and can interact with both its platelet binding sites, glycoprotein Ib-IX and glycoprotein IIb-IIIa. Fibrinogen is not involved in high shear-induced aggregation which, in fact, occurs normally in patients with severe afibrinogenemia. Thus, von Willebrand factor in the absence of exogenous agonists can mediate platelet aggregation in experimental conditions that may mimic the hemorheological situation of partially occluded arteries. This pathway of platelet aggregation involving only one adhesive ligand and two membrane adhesion receptors may play a relevant role in thrombogenesis.