miR-320a在动脉粥样硬化中对内皮功能的调控作用及机制研究

项目名称： miR-320a在动脉粥样硬化中对内皮功能的调控作用及机制研究

项目编号： No.31200594

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 生物物理、生化与生物分子学、生物力学与组织工程

项目作者： 陈琛

作者单位： 华中科技大学

项目金额： 23万元

中文摘要： 动脉粥样硬化是引起多种临床心血管事件的病理生理基础之一，但其具体病理生理机制尚未完全阐明。microRNAs（miRNAs）是一类新发现的在多种生物学进程中具有重要调控作用的非编码RNA。研究表明，miRNA在细胞增殖、凋亡、炎症、脂质代谢和免疫应答等多种与动脉粥样硬化相关的病理生理过程中发挥重要作用，我们推测存在一类miRNAs在动脉粥样硬化发生发展的各种关键环节中具有重要调控作用。在前期研究中，我们采用芯片技术筛选出动脉粥样硬化相关的miRNA 特异性表达谱，并已验证；本项目中，我们将从多角度研究筛选出的miR-320a对内皮细胞生物学效应的影响；并在经典的动脉粥样硬化动物模型中研究miR-320a的体内整体效应；最后通过生物信息学方法和经典的分子生物学方法预测并确定miR-320a的上下游分子信号通路，为动脉粥样硬化的防治和针对miRNA的靶向治疗研究提供重要的的理论依据和实验基础。

中文关键词： miRNA；动脉粥样硬化；炎症反应；内皮功能；

英文摘要： Atherosclerosis may lead to a variety of clinical cardiovascular events, but the underlying pecific pathophysiological mechanisms are not yet fully understood. miRNAs are a class of newly discovered regulatory non-coding RNA, participate in a variety of important biological process. Researches showed that miRNA play important roles in cell proliferation, apoptosis, inflammation, lipid metabolism and immune response, which are associated with atherosclerosis relevant pathophysiological processes. We hypothesized that there are a class of miRNAs involve in various key regulations of atherosclerosis development. In the previous study, we used the microarray to screen out the atherosclerosis related specific circulating miRNA expression profiles, and then validated it in a second cohort. In this project, we selected miR-320a from the previous data. Firstly, measured its effects on apoptosis, proliferation and other biological functions in endothelial cell. Secondly, classic animal models of atherosclerosis was used in in vivo study of the overall effects of miR-320a. Finally, bioinformatics methods and classical molecular biology methods were adopted to predict and identify the upstream and downstream molecular signaling targets of miR-320a. This work will provide important theoretical and experimental basis for m

英文关键词： miRNA；atherosclerosis；inflammantion；endothelial function；