Stra13对心肌肥厚的作用及其机制研究

心肌肥厚是多种心血管疾病向心力衰竭发展的重要病理过程，然而目前尚无有效的防治措施。心肌能量代谢在心肌肥厚的发生发展中发挥关键作用。Stra13是一个新发现的bHLH类转录因子，Stra13能够调节多种基因的转录活性，在能量代谢和炎症反应等生命活动中发挥重要作用。本项目前期研究发现Stra13的表达在心肌肥厚模型中显著上升，且Stra13在心肌细胞肥大过程中能够调节ATP的产生，而Stra13基因敲除会减轻压力负荷诱导的小鼠心肌肥厚。基于上述发现，我们推测Stra13可能通过对心肌能量代谢的调节参与心肌肥厚的进程。本项目拟从小鼠Stra13功能增强和功能缺失等多角度，在动物、细胞和分子等多水平，充分解析Stra13对心肌肥厚的作用及其机制，明确心肌能量代谢是否为Stra13调控心肌肥厚的关键机制，并探索以Stra13作为治疗靶点在心肌肥厚中的应用价值，为开发新型心肌肥厚治疗药物提供理论依据。

Cardiac hypertrophy is the common pathological process of various cardiovascular diseases toward to heart failure, now no effective strategies can be selected to prevent and reverse the process in our clinical practice. Cardiac energy metabolism is thought to play an important role during the process of cardiac hypertrophy and is expected to be a novel target for the treatment of cardiac hypertrophy. Stra13（Stimulated with retinoic acid 13）is a newly found basic helix-loop-helix transcription factor, its principal role has been determined in energy metabolism and inflammatory response. However, the role of Stra13 in cardiac hypertrophy is still unclear. In our preliminary experiments, our research group found that the expression of Stra13 was upregulated in hypertrophic myocardiunm, and Stra13 regulates ATP production during cardiomyocyte hypertrophy, moreover, cardiac hypertrophy was significantly aggravated in Stra13 knockout mice, suggesting a potential involvement of Stra13 in cardiac hypertrophy. In the following study, we are going to use gain- and loss-of-function approaches in animal, cellular, and molecular experiments to dissect the underlying regulatory mechanism of Stra13 in cardiac hypertrophy. Moreover, we are going to try the strategy of Stra13 inhibition in the treatment for cardiac hypertrophy. The outcomes of this project will provide new avenues for the treatment of cardiac hypertrophy and the related heart diseases.