心血管疾病是威胁人类健康的头号杀手，是我国疾病患者的第一大致死原因。预防和治疗心血管疾病是医学和生物学研究亟待解决的问题。我们最新的研究发现MADD蛋白具有抗心肌肥大功能，同时发现非编码RNA参与了MADD调控心肌肥大通路。据此，本项目拟研究MADD和非编码RNA在调节心肌细胞功能中的作用及其分子机制。研究内容包括：（1）探究miR-23a在心肌细胞肥大中的功能以及与其他microRNA的相互作用；（2）研究MADD对心肌细胞肥大的调控作用；（3）在miR-23a敲除鼠中研究miR-23a调控心肌细胞肥大的分子机制；（4）在MADD心脏特异性转基因鼠和条件性敲除鼠中研究MADD对心肌细胞肥大的抑制作用；（5）研究miR-23a是否能通过作用于MADD进而调控心肌细胞肥大。本研究对于丰富和完善心脏分子和细胞生物学具有重要的理论意义，同时为探究心肌肥大及心衰的预防和治疗开辟一个新的方向。

Cardiovascular diseases have become the top killer of human health and life as well as the first major cause of death in China. Prevention and treatment of cardiovascular disease is urgently needed to be addressed.Our latest results showed that protein MADD could suppress myocardial hypertrophy which involved of non-coding RNA. Hereby, this project is aimed to explore the role of MADD and non-coding RNA in regulating cardiomyocyte function and the underlying mechanism. Our research contents includes: (1)exploring the role of miR-23a in cardiomyocyte hypertrophy and the interaction with other microRNAs; (2)studying regulation function of MADD in cardiomyocyte hypertrophy; (3)adopting miR-23a knockout mouse model to investigate the mechanism in which miR-23a regulate myocardial hypertrophy; (4)studying the role of MADD during myocardial hypertrophy in MADD cardiac specificity of transgenic mouse and conditional knockout mouse; (5)exploring whether miR-23a could regulate cardiomyocyte hypertrophy through targeting MADD. This project will enrich and improve molecular and cellular biology of heart and open up a new field in exploring myocardial hypertrophy prevention and treatment method, showing important practical significance.