运动可诱导生理性心肌肥厚防治心力衰竭。环状RNA在生理性心肌肥厚中的作用尚不清楚。我们前期对游泳小鼠心脏进行环状RNA测序，筛选到一个保守的环状RNA circRNA_10681（命名为circ-ECHR）。Circ-ECHR在生理性心肌肥厚显著升高，在病理性心肌肥厚不变，干扰circ-ECHR会减小心肌细胞面积和抑制其增殖，提示其可能参与调控生理性心肌肥厚。我们鉴定出miR-141-5p是circ-ECHR的潜在下游分子。本项目拟在细胞和动物整体水平进行功能获得性和缺失性实验，明确circ-ECHR与生理性心肌肥厚的关系。然后通过功能逆转实验，明确circ-ECHR是否通过miR-141-5p调控生理性心肌肥厚。最后，探索circ-ECHR上调是否可以防治缺血再灌注损伤所致的心室重构和心力衰竭。本研究将鉴定出一个介导运动诱导的生理性心肌肥厚的关键环状RNA，为心力衰竭的干预提供新靶点。

Exercise can induce physiological cardiac growth and protect heart failure. The role of circular RNAs (circRNAs) in physiological cardiac growth is unclear. We previously generated RNA sequencing data from exercise induced physiological cardiac growth hearts and controls, and detected at least 12000 circRNA candidates. We further characterized one abundant and conserved circRNA_10681, termed Exercise induced Cardiac Hypertrophy related-circular RNA(circ-ECHR). Circ-ECHR was upregulated in exercise induced physiological cardiac growth, while was not changed in pathological cardiac growth. Circ-ECHR knockdown could decrease cardiomyocytes size and inhibit cardiomyocytes proliferation, indicating that circ-ECHR might regulate physiological cardiac growth. In addition, miR-141-5p was identified as a downstream target of circ-ECHR. In this project, we firstly aim to perform circ-ECHR gain- and loss-of-function assays based on cardiomyocytes and swim mice to clarify the role of circ-ECHR in physiological cardiac growth. Secondly, whether circ-ECHR regulates physiological cardiac growth via targeting miR-141-5p will be elucidated by conducting functional rescue assays. Finally, we will investigate whether elevated circ-ECHR could protect against adverse ventricular remodeling and heart failure induced by cardiac ischemia/reperfusion injury in vivo. Our project will identify a critical circRNA contributing to exercise induced physiological cardiac growth and provide a novel therapeutic strategy for heart failure.