MicroRNA-17对血管损伤后内皮修复的作用及机制研究

项目名称： MicroRNA-17对血管损伤后内皮修复的作用及机制研究

项目编号： No.81200156

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学一处

项目作者： 陈静

作者单位： 武汉大学

项目金额： 23万元

中文摘要： 血管损伤内皮修复延迟是PCI术后支架内再狭窄和晚期支架内血栓发生的共同病理生理基础，选择具有"内皮特异性"及"多位点性"的治疗靶点，对于有效改善内皮修复具有重要意义。以往研究以及我们的前期研究发现抗血管形成的microRNA-17在特异性调控血管内皮细胞功能中起重要作用，其表达持续升高可能与血管损伤后内皮修复延迟密切相关。我们利用生物信息学方法发现microRNA-17调控内皮功能的主要机制与CBP途径和VEGF-A/VEGF-R介导的下游3条信号通路有关。因此本项目主要研究内容包括 1）阐明microRNA-17调控内皮细胞的内在机制，探讨microRNA-17是否在"内皮特异性"和"干预基因多样性"方面更具优势；2）建立大鼠颈总动脉球囊损伤模型，通过局部下调损伤血管处microRNA-17表达，评价损伤血管再狭窄程度、内皮化进程和生理功能恢复程度，为冠脉损伤修复提供新的治疗策略。

中文关键词： microRNA-17；内皮修复；血管损伤；血管内皮细胞；

英文摘要： Delayed endothelium recovery is the common physiopathological factor for in-stent restenosis and late stent thrombosis after PCI. Therefore it is important to choose the effective therapeutic approach with endothelium specificity and multiple target sites for the improvement of endothelium recovery. Previous studies and our preliminary research work found that microRNA-17 might be one of the key microRNAs to regulate the functions of vascular endothelial cell (EC). In addition, the highly persistent expression of microRNA-17 is associated with delayed endothelium recovery after vascular injury. Moreover, we hypothesized that CBP pathway and the three down-stream pathways of VEGF-A/VEGF-R were the main mechanisms for microRNA-17 to regulate EC function through bioinformatics approaches. Thus, our research is mainly focused on 1) clarification of the underlying mechanisms with which microRNA-17 regulated EC functions; investigation of the superiority of microRNA-17 on endothelium specificity and multiple target sites; 2) examination of restenosis, endothelialization and physiologic function after vascular injury with down-regulation of microRNA-17 expression in the rat carotid artery balloon injury model. The purpose of this project is to provide a promising therapeutic strategy for coronary artery injury.

英文关键词： microRNA-17；endothelium recovery；vascular injury；vascular endothelial cell；