血小板在心脑血管栓塞性疾病的形成和发展中起到了极为关键的作用。血小板膜上糖蛋白GPIb-IX-V作为一种重要的受体，与配体vWf结合，可以引发胞内信号事件导致血小板在病理性血管损伤部位粘附、活化、聚集。近年来，随着我们对糖蛋白GPIb-IX-V受体生物学功能研究的逐渐深入，发现该受体及其介导信号在动脉性血栓形成中具有决定性作用。在本申请中，我们将利用多种基因敲除小鼠，围绕PI3K/Akt通路关键信号分子在GPIb-IX-V介导血小板活化和动脉血栓形成中的作用及其机制展开研究。并根据前期研究数据，尝试寻找GPIb-IX-V受体与其配体vWf结合的特异性阻断剂。本研究将有助于阐述动脉血栓形成过程中的血小板活化分子调控理论，为临床治疗动脉血栓性疾病提供新思路。

Platelets play an important role in cardiovascular thromboembolic disease. Platelet membrane glycoprotein GPIb-IX-V, as a major receptor of vWf, can trigger intracellular signaling events leading to platelet adhesion, aggregation and secretion at vascular injury site. Recently, a series of our studies revealed that GPIb-IX-V receptor and it-mediated signals play critical functions in arterial thrombosis. In this application, we will develop a variety of PI3K/Akt pathway signaling molecules knockout mice, and investigate the mechanism of PI3K/Akt pathway in the GPIb-IX-V/vWf-mediated platelet activation and arterial thrombosis. And we will develop a new strategy for GPIb-IX-V receptor specificity inhibitor based on preliminary discovery of a natural peptide target on GPIbα/vWf. The results derived from this application will enrich our understanding of the molecular regulation of arterial thrombosis and provide new methods for the clinical treatment of arterial thrombotic disease.