Sachs Ulrich J H, Nieswandt Bernhard
Rudolf Virchow Center, Deutsche Forschungsgemeinschaft Research Center for Experimental Biomedicine, University of Würzburg, Germany.
Circ Res. 2007 Apr 13;100(7):979-91. doi: 10.1161/01.RES.0000261936.85776.5f.
Platelets play a central role in hemostasis, but also in atherothrombosis, as they rapidly adhere to tissue and to one another as a response to any vascular injury. This process involves a large number of surface receptors, signaling pathways, and enzymatic cascades as well as their complex interplay. Although in vitro experiments proved successful in both identifying new receptors and pathways and developing potent and selective antithrombotic drugs, in vitro research cannot mimic the myriad hemodynamic and spatiotemporal cellular and molecular interactions that occur during the generation and propagation of thrombi in vivo. Animal models, and, with the availability of genetically modified mouse strains and of modern intravital imaging techniques, mouse models in particular, have opened new ways to identify both individual roles and the interplay of platelet proteins in complex in vivo settings. In vivo models revealed the important role of, eg, Gas6 or blood coagulation factor XII in thrombus formation, and results obtained in in vivo models raised the interesting possibility that (physiologic) hemostasis and (pathologic) thrombosis might represent 2 mechanistically different processes. This review summarizes in vivo findings that contributed significantly to our understanding of hemostatic and thrombotic processes and which may help to guide future research.
血小板在止血过程中发挥着核心作用，在动脉粥样硬化血栓形成中也同样如此，因为它们会对任何血管损伤做出反应，迅速黏附于组织并相互黏附。这一过程涉及大量表面受体、信号通路和酶促级联反应以及它们之间复杂的相互作用。尽管体外实验在识别新受体和新通路以及开发强效和选择性抗血栓药物方面取得了成功，但体外研究无法模拟体内血栓形成和传播过程中发生的无数血流动力学以及时空细胞和分子相互作用。动物模型，尤其是随着基因工程改造小鼠品系和现代活体成像技术的出现，小鼠模型为在复杂的体内环境中识别血小板蛋白的个体作用及其相互作用开辟了新途径。体内模型揭示了例如Gas6或凝血因子XII在血栓形成中的重要作用，并且在体内模型中获得的结果提出了一个有趣的可能性，即（生理性）止血和（病理性）血栓形成可能代表两个机制不同的过程。本综述总结了对我们理解止血和血栓形成过程有重大贡献且可能有助于指导未来研究的体内研究结果。
