心肌梗死（MI）后机械应力改变是心室重塑的重要因素。Piezo1是机械应力敏感离子通道，对钙离子通透性高，其在MI后心室电重构中作用尚无报道。我们预实验发现心衰病人心脏Piezo1表达升高；心肌细胞Piezo1敲除抑制小鼠MI后肌浆网钙泵SERCA2表达，心室程序性电刺激室速室颤阈值增高、诱发率降低，生存率提高；Piezo1敲除的心肌细胞诱发的钙瞬变峰值下降。因此，我们推测Piezo1介导SERCA2-Ca2+调控MI后心室电重构。本研究拟应用心肌细胞Piezo1敲除或腺相关病毒过表达心脏Piezo1的小鼠，深入阐明Piezo1调控MI后心室电重构的作用；观察Flex Cell细胞牵拉模型和药物刺激对分离的成年心肌细胞钙稳态、动作电位、SERCA2/Ca2+信号的影响；运用转录组测序和双分子荧光技术从转录及结构水平阐明Piezo1调控SERCA2-Ca2+的机制，为寻找新靶点提供理论依据。

The alteration of mechanical stress after myocardial infarction (MI) is important in the progression of cardiac remodeling. Piezo1, a newly-identified ion channel which is sensitive to mechanical stress, shows strong permeability to calcium. The role of Piezo1 in cardiac electrical remodeling after MI is unclear. Our preliminary data found that: Piezo1 expression was elevated in human failing hearts. Mice with conditional knockout of Piezo1 in cardiomyocyte showed decreased risk of arrhythmia and mortality after MI, which was evaluated by electrical pre-stimulation in ventricule. Besides, cardiomyocyte Piezo1 knockout mice exhibited decreased SERCA2 expression, which is a calcium pump in sarcoplasmic reticulum, as well as the peak of calcium transient. Hence, we hypothesized that cardiomyocyte-Piezo1 regulates cardiac remodeling after MI through SERCA2-Ca2+. This project will focus on exploring the role and mechanism of Piezo1 in cardiac remodeling by using conditional Piezo1 knockout mice and Piezo1 over-expressed mice. Flex cell model and drug stimulation will also be employed in cultured Piezo1 knockout cardiomyocytes. The indexes including Ca2+, action potential and SERCA2/Ca2+ will be evaluated. Finally, RNA-sequencing and bimolecular fluorescence will be applied to clarify the transcriptional and structural mechanisms of Piezo1 regulating SERCA2-Ca2+.