SIRT1-mediated YAP deacetylation suppresses myocardial hypertrophy in diabetic cardiomyopathy

Sirtuin 1 (SIRT1) is a nicotinamide adenosine dinucleotide-dependent deacetylase regulating various cellular processes. Yes-associated protein (YAP) is a transcription cofactor of the Hippo pathway which is implicated in cardiac remodelling. However, the effects of SIRT1 and YAP on diabetic cardiomyopathy (DCM)-induced cardiac hypertrophy remain unclear. In this study, the relationship of SIRT1 and YAP on cardiac hypertrophy in DCM was investigated using an overexpressing rat model and overexpression/knockdown H9c2 cardiomyocytes. We found that in DCM rat hearts and high glucose-induced H9c2 cardiomyocytes, SIRT1 expression significantly decreased, YAP expression significantly increased, and the overexpression of SIRT1 decreased the acetylation level of YAP and reduced its nuclear translocation, thus alleviating myocardial hypertrophy. Furthermore, in the H9c2 cardiomyocytes model, YAP downregulation attenuated high glucose-induced H9c2 cardiomyocyte hypertrophy by inhibiting the PI3K/AKT pathway. Our findings suggest that YAP is closely associated with cardiac hypertrophy in DCM through the PI3K-Akt signalling pathway, and its acetylation modification influences the nuclear translocation of YAP; SIRT1 overexpression alleviated cardiac hypertrophy in DCM by mediating YAP deacetylation.