研究表明昼夜节律紊乱和多种心血管疾病有密切关系，但昼夜节律因子在心力衰竭（心衰）中的作用机制不清楚。我们既往研究表明昼夜节律因子DEC1在调控细胞周期蛋白E及增殖中发挥重要作用。我们前期实验也发现DEC1表达水平在苯肾上腺素(PE)处理的心肌细胞和主动脉缩窄(TAC)术后的心肌中明显降低。相反，在体外心肌细胞中过表达DEC1可明显抑制PE引起的细胞凋亡和肥大。用腺相关病毒过表达DEC1可显著改善TAC引起的小鼠心衰和心肌细胞凋亡；免疫共沉淀发现DEC1可与胰岛素生长因子1受体（IGF1R）相互作用。但仍需深入研究DEC1调节心衰的分子机制。本课题拟在心肌特异DEC1转基因或敲除小鼠，过表达或干扰DEC1的心肌细胞中，研究DEC1在心衰和重构（心脏收缩功能、细胞大小、凋亡及纤维化）及体外心肌细胞收缩力中的作用；明确DEC1调控IGF1R、凋亡及心衰的分子机制。为寻找潜在的新药靶点提供新依据。

Many studies have demonstrated that circadian rhythm disorder is associated with cardiovascular disease. However, the role of circadian rhythm genes in the development of heart failure remains unclear. Our published data indicate that circadian rhythm gene DEC1 plays a critical role in regulating cyclin E and cell growth. Our recent preliminary results indicated that the expression of DEC1 was significantly decreased in phenylephrine (PE)-treated cardomyocytes and transverse aortic constriction (TAC)-treated heart. In contrast, Overexpression of DEC1 in cardiomyocytes markedly inhibited PE-induced cardiomyocyte hypertrophy and apoptosis. Moreover, rAAV9-mediated overexpression of DEC1 in mice markedly suppressed TAC-induced heart failure. Co-immunoprecipitation assay showed that DEC1 interacted with IGF1R. In this study, with cardiac-specific knockout and overexpressing DEC1 mice as well as cultured cardiomyocytes in vitro, we will further study the molecular mechanism by which DEC1 regulates heart failure and remodeling, including cardiac contractile function, cardiomyocyte size, apoptosis and fibrosis; elucidating how DEC1 interacts with IGF1R and then regulates heart failure. Taken together, our results will provide novel evidence for understanding the role and mechanism of DEC1 in regulating heart failure, thus providing new evidence for potential therapeutic target of heart failure.