血管再狭窄是一类源于新生内膜增殖的血管病变，是影响血管置换术和血管成形术远期疗效的主要原因。血管重建术后形成炎症环境引发的血管细胞增殖、迁移行为的改变的是血管再狭窄发生的根本原因。项目前期研究CLEC-2在PCI血管成形术后发生血管再狭窄的患者中有显著的升高；同时血管重建术小鼠血管再狭窄模型的结果显示发现血小板CLEC-2受体抑制抗体能够显著降低血管再狭窄小鼠模型新生内膜厚度及面积，这些结果提示CLEC-2受体与血管再狭窄可能存在密切的关联。本项目拟在前期工作的基础上，利用PCI术后患者的血浆样本、体内静脉移植物血管再狭窄模型、血管平滑肌及血管内皮细胞增殖迁移模型，系统研究和确立血小板CLEC-2受体在血管再狭窄中的作用效应及血管细胞生物学行为中的调控作用，并利用血小板聚集和分泌模型揭示CLEC-2受体的作用机制，藉此为以CLEC-2为作用靶点的血管再狭窄治疗新策略提供实验依据和理论基础。

Restenosis, characterized by neointimal hyperplasia, is the major factor of the long-term effect of graft bypass surgery and percutaneous transluminal angioplasty. Inflammatory microenvironment caused by vessel revascularization procedures could result in the abnormal proliferation and migration of vascular cells, which is considered as the fundamental cause for vascular restenosis. Our preliminary studies have shown that significantly increased plasma level of CLEC-2 was found in patients with the presentation of restenosis after percutaneous coronary intervention (PCI); moreover, we found that CLEC-2 inhibitory antibody could significantly decreased intimal thickness and intimal area in a mouse model of vein graft bypass surgery, suggesting a possible close relationship between CLEC-2 receptor and restenosis. Based on these results, we plan to systematically investigate and identify the regulatory role of CLEC-2 receptor in restenosis and on the biological behavior of vascular cells by using plasma sample of PCI patients, vein graft bypass model, and proliferation and migration model; furthermore, the regulatory mechanism of CLEC-2 will be elucidated by using in vitro platelet aggregation and secretion under the risk factor of restenosis. This results obtained from this project will provide experimental evidence and theory basis to employ CLEC-2 as a potential therapeutic target in treatment of restenosis.