Andrews R K, Berndt M C
Hazel and Pip Appel Vascular Biology Laboratory, Baker Medical Research Institute, Melbourne, Australia.
Toxicon. 2000 Jun;38(6):775-91. doi: 10.1016/s0041-0101(99)00187-7.
In thrombosis, platelet aggregation is initiated by a specific membrane glycoprotein (GP) Ib-IX-V complex binding to its adhesive ligand, von Willebrand factor, in the matrix of ruptured atherosclerotic plaques or in plasma exposed to high hydrodynamic shear stress. This process closely resembles normal haemostasis at high shear, where GP Ib-IX-V-dependent platelet adhesion to von Willebrand factor in the injured blood vessel wall initiates platelet activation and integrin alphaIIb beta3 (GP IIb-IIIa)-dependent platelet aggregation. At low shear, other receptors such as those that bind collagen, the integrin alpha2beta1 (GP Ia-IIa) or GP VI, mediate platelet adhesion. Recently, snake venom proteins have been identified that selectively modulate platelet function, either promoting or inhibiting platelet aggregation by targeting GP Ib-IX-V, alpha2beta1, GP VI, alphaIIb beta3, or their respective ligands. Interestingly, these venom proteins typically belong to one of two major protein families, the C-type lectin family or the metalloproteinase-disintegrins. This review focuses on recent insights into structure-activity relationships of snake venom proteins that regulate platelet function, and the ways in which these novel probes have contributed in unexpected ways to our understanding of the molecular mechanisms underlying thrombosis.
在血栓形成过程中，血小板聚集是由一种特定的膜糖蛋白（GP）Ib-IX-V复合物与它的黏附配体血管性血友病因子结合启动的，这种结合发生在破裂的动脉粥样硬化斑块基质中或暴露于高流体动力剪切应力的血浆中。这一过程与高剪切力下的正常止血过程非常相似，在正常止血过程中，依赖GP Ib-IX-V的血小板与受损血管壁中的血管性血友病因子黏附会启动血小板活化以及依赖整合素αIIbβ3（GP IIb-IIIa）的血小板聚集。在低剪切力下，其他受体如那些结合胶原蛋白的受体、整合素α2β1（GP Ia-IIa）或GP VI介导血小板黏附。最近，已鉴定出一些蛇毒蛋白，它们通过靶向GP Ib-IX-V、α2β1、GP VI、αIIbβ3或它们各自的配体来选择性调节血小板功能，促进或抑制血小板聚集。有趣的是，这些蛇毒蛋白通常属于两个主要蛋白家族之一，即C型凝集素家族或金属蛋白酶-解整合素家族。本综述重点关注调节血小板功能的蛇毒蛋白的结构-活性关系的最新见解，以及这些新型探针以意想不到的方式有助于我们理解血栓形成潜在分子机制的方式。
