心肌肥厚发病机制及其调控新靶点：lncRNAs

项目名称： 心肌肥厚发病机制及其调控新靶点：lncRNAs

项目编号： No.81473213

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 许超千

作者单位： 牡丹江医学院

项目金额： 60万元

中文摘要： 心肌肥厚是导致心力衰竭和心源性猝死的重要危险因子之一,其发病因素复杂，机制尚不十分清楚，导致临床治疗效果不佳。最新研究发现长链非编码RNAs（lncRNAs）与多种疾病的发生密切相关。我室新近研究结果显示，心肌肥厚时lncRNAs表达谱显著改变，表明lncRNAs与心肌肥厚发生、发展密切相关，然而这些异常表达的lncRNAs通过何种方式参与了心肌肥厚的调控？是否可以作为心肌肥厚药物治疗的新靶点？这些尚不清楚。本课题将利用基因芯片检测心肌肥厚发生后lncRNAs的表达谱变化，通过生物信息学、分子生物学等技术研究lncRNAs在心肌肥厚中对靶基因的调控网络通路、特点、规律及机制，揭示lncRNAs对心肌肥厚发生、发展的重要作用，为心肌肥厚的基础研究、药物研发与临床防治提供重要的理论依据。

中文关键词： 心肌肥厚；靶点；长链非编码RNA；心肌细胞重构

英文摘要： Myocardial hypertrophy is an independent and major risk factor for heart failure and cardiac sudden death. In the past, major efforts have been made to retard the transition from hypertrophy to failure. The view on cardiac hypertrophy, however, has been recently renewed that hypertrophy represent a pathological condition that should be and can be reversed. To make this happen, thorough understanding of the nature of cardiac hypertrophy is necessary. Recently, a new class of non-coding RNAs, long non-coding RNAs (lncRNAs) has been identified in a variety of eukaryotes. Although most remain functionally uncharacterized biological dark matter, lncRNAs have garnered considerable attention for their diverse roles in human biology. Aberrant lncRNA expression is found to be associated with human diseases such as cancers, Alzhemier's disease and cardiovascular diseases. We hypothesized that (1) a subset of lncRNAs are deregulated in their expression in hypertrophied heart; (2) some of these deregulated lncRNAs play key roles in regulating cardiac hypertrophy, either favoring or mitigating, being a new molecular mechanism for cardiac hypertrophy and heart failure; and (3) normalization of expression of these key lncRNAs can reverse the adverse remodeling process of hypertrophy. The study proposed aims to examine this hypothesis. Completion of the study should unravel the pathophysiological functions of lncRNAs in cardiac hypertrophy, elucidate the target gene network of lncRNAs related to hypertrophy signaling, decoding the mechanisms for deregulation of these lncRNAs, and lay the groundwork for the development of new strategies for reversing cardiac hypertrophy and preventing heart failure by interfering the expression of the lncRNAs key to cardiac function.

英文关键词： cardiac hypertrophy;targets;lncRNAs;cardiac myocytes remodeling