重组腺相关病毒介导的miR-21-3p在高血压中的作用及机制研究

项目名称： 重组腺相关病毒介导的miR-21-3p在高血压中的作用及机制研究

项目编号： No.81500327

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 王峰

作者单位： 华中科技大学

项目金额： 18万元

中文摘要： 高血压是心脑血管疾病最重要的危险因素，预防和控制高血压能显著降低心脑血管疾病的发病率和死亡率。但目前高血压的控制率极低，高血压的发病率仍在逐年增加，因而迫切需要寻求新的治疗方法。MicroRNA是一类非编码的小RNA，它能在转录后水平调控基因的表达，越来越多的证据表明miRNAs在心血管疾病中的发挥着重要作用。我们的前期研究发现血浆miR-21-3p在高血压患者及高血压模式动物中存在差异性表达，重组腺相关病毒介导的miR-21-3p能显著降低自发性高血压大鼠（SHRs）血压，但其机制尚未明确。本项目重在探讨miR-21-3p对高血压模式动物(SHRs)血压的影响及其具体的上下游分子信号通路，从而阐明miR-21-3p在高血压中的作用及机制，为高血压的防治提供新的思路，为研究高血压的microRNA靶向治疗药物提供新的理论依据。

中文关键词： miRNAs；高血压；重组腺相关病毒；转录因子；基因治疗

英文摘要： Hypertension is the most important risk factor for a wide variety of cardiovascular diseases. Prevention and control of hypertension can significantly reduce the morbidity and mortality of cardiovascular diseases. However, the control rate of hypertension is very low right now，and the morbidity of hypertension is still increasing year by year, so some new treatments are urgently needed for treatment of hypertension. MicroRNAs are endogenous small noncoding RNAs, and they can regulate the expressions of protein-coding genes at the posttranscriptional level. Recent evidences demonstrated that miRNAs play prominent roles in various cardiovascular diseases. In our previous studies, the differential expression of plasma miR-21-3p were found in both hypertension patients and hypertensive animal models. Recombinant adeno-associated virus mediated delivery of miR-21-3p induced a persistent and remarkable attenuation of hypertension in spontaneously hypertensive rats (SHRs). However the mechanism of the hypotensive effect of miR-21-3p is still unknown. In order to comprehensively clarify the functions and mechanisms of miR-21-3p in hypertension, this study focuses on clarifying the role and mechanisms of miR-21-3p in hypertension and identifying the upstream and downstream molecular signaling targets of miR-21-3p in hypertension. This project will provide important theoretical basis for miRNA targeted therapy for prevention and treatment of hypertension.

英文关键词： miRNAs; Hypertension; Recombinant adeno-associated virus;Transcription factor;Gene therapy