UMR-S949 Inserm-Université de Strasbourg, Strasbourg, France.
J Thromb Haemost. 2011 Apr;9(4):779-89. doi: 10.1111/j.1538-7836.2011.04218.x.
The FeCl(3)-induced vascular injury model is widely used to study thrombogenesis in vivo, but the processes leading to vascular injury and thrombosis are poorly defined.
The aim of our study was to better characterize the mechanisms of FeCl(3)-induced vascular injury and thrombus formation, in order to evaluate the pathophysiological relevance of this model.
FeCl(3) was applied at different concentrations (from 7.5% to 20%) and for different time periods (up to 5 min) to mouse carotid or mesenteric arteries.
Under all the conditions tested, ultrastructural analysis revealed that FeCl(3) diffused through the vessel wall, resulting in endothelial cell denudation without exposure of the inner layers. Hence, only the basement membrane components were exposed to circulating blood cells and might have contributed to thrombus formation. Shortly after FeCl(3) application, numerous ferric ion-filled spherical bodies appeared on the endothelial cells. Interestingly, platelets could adhere to these spheres and form aggregates. Immunogold labeling revealed important amounts of tissue factor at their surface, suggesting that these spheres may play a role in thrombin generation. In vitro experiments indicated that FeCl(3) altered the ability of adhesive proteins, including collagen, fibrinogen and von Willebrand factor, to support platelet adhesion. Finally, real-time intravital microscopy showed no protection against thrombosis in GPVI-immunodepleted and β(1)(-/-) mice, suggesting that GPVI and β(1) integrins, known to be involved in initial platelet adhesion and activation, do not play a critical role in FeCl(3)-induced thrombus formation.
This model should be used cautiously, in particular to study the earliest stage of thrombus formation.
三氯化铁(FeCl(3))诱导的血管损伤模型广泛用于体内血栓形成的研究,但导致血管损伤和血栓形成的过程尚未完全阐明。
本研究旨在更好地描述 FeCl(3)诱导的血管损伤和血栓形成的机制,以评估该模型的病理生理相关性。
将不同浓度(7.5%至 20%)和不同作用时间(最长 5 分钟)的 FeCl(3)应用于小鼠颈动脉或肠系膜动脉。
在所有测试条件下,超微结构分析显示 FeCl(3)扩散穿过血管壁,导致内皮细胞剥脱而内层不暴露。因此,只有基底膜成分暴露于循环血细胞,可能促成血栓形成。FeCl(3)作用后不久,内皮细胞上出现大量充满铁离子的球体。有趣的是,血小板可以黏附在这些球体上并形成聚集体。免疫金标记显示其表面存在大量组织因子,提示这些球体可能在凝血酶生成中发挥作用。体外实验表明,FeCl(3)改变了包括胶原蛋白、纤维蛋白原和血管性血友病因子在内的黏附蛋白支持血小板黏附的能力。最后,实时活体显微镜检查显示,在 GPVI 免疫耗竭和 β(1)(-/-)小鼠中没有对血栓形成起到保护作用,表明已知参与初始血小板黏附和激活的 GPVI 和 β(1)整合素在 FeCl(3)诱导的血栓形成中不起关键作用。
该模型应谨慎使用,特别是在研究血栓形成的最初阶段时。