心力衰竭中血管稳态和重构的转录后调控机制研究

项目名称： 心力衰竭中血管稳态和重构的转录后调控机制研究

项目编号： No.91439203

项目类型： 重大研究计划

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 汪道文

作者单位： 华中科技大学

项目金额： 270万元

中文摘要： 心力衰竭是不同的心血管疾病发展到终末阶段的临床综合征，其预后差，死亡率高。研究表明，血管稳态功能从多个方面参与心力衰竭病理生理调控过程，包括血管生成、血管张力调节、出血/止血功能、抗氧化、抗炎等。我们前期研究发现，miRNAs为代表的非编码RNAs在内皮细胞功能、血管生成、糖脂代谢、氧化应激、内质网应激、等与心力衰竭密切相关的病理生理过程中发挥重要作用。在本项目中我们将以心力衰竭时心肌血管稳态和重构障碍及其转录后调控机制的研究为中心，在人心力衰竭样本、模式动物和细胞水平利用分子生物学、病理生理学、基因组学、系统生物学、分子影像学、化学、生物信息学等手段，研究阐明血管结构与功能稳态，尤其是血管新生障碍在心力衰竭过程中调控的关键非编码RNAs的作用机制、信号和网络模式。本研究将为心力衰竭发病机制提供新学说，为研究心力衰竭新的预防及治疗策略和方法提供依据。

中文关键词： 心肌血管新生；非编码RNAs；心力衰竭；血管稳态；转录后调控

英文摘要： Heart failure is the end stage clinical syndrome of various cardiovascular diseases, which has poor prognosis and high mortality. Studies have shown that vascular homeostasis and remodeling participate in the pathophysiology of heart failure processes, such as angiogenesis, tension adjustment, hemorrhage/hemostatic function, antioxidant and anti-inflammatory. Our previous studies have found that non-coding RNAs, especially miRNAs played key roles in endothelial function, angiogenesis, lipid metabolism, oxidative stress, and endoplasmic reticulum stress, which are closely associated with the pathophysiology of heart failure processes. In this project, we will mainly investigate the post-transcriptional regulation mechanisms of endothelial function and myocardial angiogenesis disorder, in the human heart samples, animal models and cultured cells using molecular biological, pathophysiological, genomic, systems biological, molecular imaging, chemistry, bioinformatic and other methods to illustrates the structure and function of vascular homeostasis, especially angiogenesis disorders in heart.failure by non-coding RNAs regulation mechanisms. This study will provide a new theory for new strategies and methods for heart failure prevention and treatment.

英文关键词： myocardial angiogenesis;non-coding RNAs;heart failure;vascular homeostasis;posttranscriptional regulation