血小板过度活化是多种心脑血管疾病发生发展及猝死的重要原因。新近研究表明，血小板活化在肺动脉高压（PH）PH中起重要作用，然其确切机制未明。申请人前期研究发现植物凝集素样氧化低密度脂蛋白受体-1（LOX-1）介导低氧PH肺动脉平滑肌细胞（PASMCs）增殖及内皮间质转化（EndMT）。我们预实验发现低氧PH时血小板活化增多，且可通过磷脂酰丝氨酸（PS）与PASMCs或肺动脉内皮细胞LOX-1结合而促进PASMCs增殖或EndMT。本项目拟通过在体动物与细胞实验，阐明血小板-血管细胞相互作用在低氧PH肺血管重构中的重要作用，并进一步探讨LOX-1介导血小板诱导PASMCs增殖机制（PS/LOX-1/TGF-β/NF-B/MMP）及EndMT机制（PS/LOX-1/PKC/STAT3/Pim-1）。本项目将有助于阐明PH的发病机制，为寻找防治PH的新靶点奠定基础。

Platelet over-activation is the important reason for the occurrence and development of many cardiovascular and cerebrovascular diseases and sudden death. Recent researches show that platelet activation plays an important role in Pulmonary hypertension (PH), but the underlying mechanisms are unknown. Our previous studies found that LOX-1 mediated PASMCs proliferation and endothelial interstitial transformation (EndMT) in hypoxia-induced PH. The pilot studies showed that platelet activation was increased in hypoxia-induced PH and PASMCs proliferation or EndMT could be promoted by phosphatidylserine (PS) binding to LOX-1 in PASMCs or pulmonary artery endothelial cells. We will be planning to explore the important role of platelets-vascular cells interaction in mediating the pulmonary vascular remodeling in hypoxia-induced PH rats, the proliferation of primary cultured rat PASMCs and EndMT. Furthermore, we will investigate the underlying mechanisms of platelets-induced PASMCs proliferation mediated by LOX-1 (focusing on PS/LOX-1/TGF-β/NF-B/MMP ) and the signaling pathway of platelets-induced EndMT mediated by LOX-1 (focusing on PS/LOX-1/PKC/STAT3/Pim-1 pathway). This study will contribute to the understanding of the pathogenesis of PH, and provide new strategies to seek for the new drugs directing at LOX-1 target.