Glycoprotein VI-dependent and -independent pathways of thrombus formation in vivo
Glycoprotein VI-dependent and -independent pathways of thrombus formation in vivo
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DOI：
10.1182/blood-2005-09-3687
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发表时间：
2006-05-15
期刊：
影响因子：
20.3
通讯作者：
Furie, Barbara C.
中科院分区：
文献类型：
--
作者：
Dubois, Christophe;Panicot-Dubois, Laurence;Furie, Barbara C.
在缺乏血小板表面GPVI的FcR γ-敲除小鼠（FcR γ（-/-））中研究了胶原受体糖蛋白VI（GPVI）在小动脉血栓形成中的作用。血栓形成与严重或轻度FeCl 3损伤。胶原蛋白暴露显着延迟和减少相比，严重FeCl 3轻度损伤。严重损伤后，FcR-γ（-/-）小鼠的初始血栓形成和血管闭塞时间比野生型小鼠延迟。与严重损伤相比，轻度损伤后野生型小鼠的血小板聚集减少。然而，在FcR γ（-/-）方面，严重或轻度损伤后血小板聚集之间几乎没有差异。这些数据表明GPVI在FeCl 3诱导的血栓形成中具有重要作用。用来匹卢定预处理野生型小鼠进一步损害了轻度FeCl 3诱导的血栓形成，证明了凝血酶的作用。野生型和FcR γ（-/-）中激光诱导的血栓形成相当。激光损伤后，胶原蛋白暴露于循环血液中检测不到。血栓大小标准化后，激光诱导血栓中的血栓相关组织因子是严重FeCl 3诱导血栓的5倍。因此，激光损伤后凝血酶对血小板的激活作用似乎比GPVI-胶原对血小板的激活作用更重要。因此，在考虑抗血栓治疗的靶点时，使用具有不同血栓形成途径的多种动物模型可能很重要。
The role of the collagen receptor glycoprotein VI (GPVI) in arteriolar thrombus formation was studied in FcR gamma-null mice (FcR gamma(-/-)) lacking platelet surface GPVI. Thrombi were induced with severe or mild FeCl3 injury. Collagen exposure was significantly delayed and diminished in mild compared with severe FeCl3 injury. Times to initial thrombus formation and vessel occlusion were delayed in FcR-gamma(-/-) compared with wild-type mice after severe injury. Platelet accumulation in wild-type mice was decreased after mild compared with severe injury. However, there was little difference between platelet accumulation after severe or mild injury in FcR gamma(-/-). These data indicate a significant role for GPVI in FeCl3-induced thrombus formation. Pretreatment of wild-type mice with lepirudin further impaired mild FeCl3-induced thrombus formation, demonstrating a role for thrombin. Laser-induced thrombus formation in wild-type and FcR gamma(-/-) was comparable. Collagen exposure to circulating blood was undetectable after laser injury. Normalized for thrombus size, thrombus-associated tissue factor was 5-fold higher in laser-induced thrombi than in severe FeCl3-induced thrombi. Thus, platelet activation by thrombin appears to be more important after laser injury than platelet activation by GPVI-collagen. It may thus be important when considering targets for antithrombotic therapy to use multiple animal models with diverse pathways to thrombus formation.