Hypoxia induces cardiomyocyte autophagy by regulating SIRT5 expression

Abstract Objective To investigate the expression of SIRT5 in myocardial hypoxia and to further explore its function during this pathological process. Material and methods We analysed the microarray dataset GSE27975 derived from the Gene Expression Omnibus (GEO) database and identified differentially expressed genes (DEGs) between hypoxic and normoxic cardiomyocytes. We divided C57BL/6J mice into two groups: the sham group and the myocardial infarction (MI) group. Heart functions were detected by echocardiogram, and heart tissue was harvested on the 3rd day after MI for the detection of autophagy and SIRT5 expression. To further study the mechanism of Sirt5 in hypoxic cardiomyocytes, we divided H9C2 cells into four groups: the control group, the hypoxia group, the Sirt5 siRNA group and the Sirt5 siRNA + hypoxia group and detected Sirt5 expression and cell autophagy. Results A total of 156 genes were highly expressed, and 185 genes were expressed at low levels between hypoxic and normoxic cardiomyocytes. SIRT5 was expressed at low levels in the hypoxia group. In vivo, we generated an MI mouse model, and heart function was decreased. The expression of SIRT5 in heart tissue was decreased after MI, while the autophagy level was increased. In vitro, after we knocked out Sirt5 in H9C2 cardiomyocytes, autophagy was significantly increased. Meanwhile the expression of p-MTOR, p-ULK1 changed, and the mitochondrial membrane potential was maintained. Conclusion Hypoxia reduced SIRT5 expression may be associated with cardiomyocytes autophagy. Knockdown Sirt5 in H9C2s could activate autophagy via mTOR/ULK1 pathway and preserve mitochondrial function.