Nieswandt B, Aktas B, Moers A, Sachs U J H
Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine, University of Würzburg, Würzburg, Germany.
J Thromb Haemost. 2005 Aug;3(8):1725-36. doi: 10.1111/j.1538-7836.2005.01488.x.
Platelets play a central role in hemostasis and thrombosis but also in the initiation of atherosclerosis, making platelet receptors and their intracellular signaling pathways important molecular targets for antithrombotic and anti-inflammatory therapy. Historically, much of the knowledge about hemostasis and thrombosis has been derived from patients suffering from bleeding and thrombotic disorders and the identification of the underlying molecular defects. In recent years, the availability of genetically modified mouse strains with defined defects in platelet function and the development of in vivo models to assess platelet-related physiologic and pathophysiologic processes have opened new ways to identify the individual roles and the interplay of platelet proteins in adhesion, activation, aggregation, secretion, and procoagulant activity in vitro and in vivo. This review will summarize key findings made by these approaches and discuss them in the context of human disease.
血小板在止血和血栓形成中起核心作用,同时也在动脉粥样硬化的起始过程中发挥作用,这使得血小板受体及其细胞内信号通路成为抗血栓和抗炎治疗的重要分子靶点。从历史上看,许多关于止血和血栓形成的知识来自患有出血和血栓性疾病的患者以及对潜在分子缺陷的鉴定。近年来,具有明确血小板功能缺陷的基因工程小鼠品系的出现以及用于评估血小板相关生理和病理生理过程的体内模型的开发,为确定血小板蛋白在体外和体内的黏附、激活、聚集、分泌和促凝活性中的个体作用及其相互作用开辟了新途径。本综述将总结这些方法取得的关键发现,并在人类疾病的背景下进行讨论。