Role of SIRT5 in Inhibition of Myocardial Hypertrophy

SIRT5 is one of the seven members of the NAD+-dependent sirtuin family of protein deacylase that is mainly present in mitochondria and regulates metabolism. In heart, SIRT5 is highly expressed and responsible for succinylation on metabolic enzymes. Although the role of SIRT5 in maintaining cardiac homeostasis under physiological stress and few potential substrates of SIRT5 have been preliminarily revealed, the regulatory network and key cellular signaling pathways involving SIRT5 in myocardial hypertrophy remain largely unknown. Here, we used an established murine model of pressure overload-induced myocardial hypertrophy caused by transverse aortic constriction (TAC) to outline the network and pathway involving SIRT5 in cardiac stress responses. Remarkably, SIRT5 KO mice had enhanced myocardial hypertrophy after TAC surgery compared with wild-type mice.