JAHA:Sirtuin 3 relieves diabetic cardiomyopathy by regulating TIGAR and myocardial metabolism

The prevalence of diabetic cardiomyopathy is increasing at an alarming rate, and although a variety of factors, including oxidative stress, apoptosis, heart fibrosis, impaired angiogenesics and glycolysis metabolism, are considered important pathophysiological factors, the basic mechanisms of diabetic cardiomyopathy are still not fully understood.
diabetic cardiomyopathy is the main cause of heart failure, it is important to identify potential therapeutic targets to reduce morbidity and mortality in diabetic patients.
recently, a team of researchers at the University of Mississippi published a paper entitled "Sirtuin 3 Alleviates Diabetic Cardiomyopathy by Regulatoring TIGAR and Cardiomyocyte Metabolism" in Journal of the American Heart Association, exploring the role of SIRT3 in glucose metabolism and heart function in myocardial cells.
SIRT3 regulates cell metabolism by deacetyl-based action of its substrates.
evidence that SIRT3 plays an important regulatory role in cardiovascular and metabolic diseases such as heart failure, diabetes and obesity.
study also showed a decrease in the expression and activity of SIRT3 in the heart of diabetics, which was associated with obesity-induced microvascular sparseness and cardiac dysfunction.
increase in SIRT3 in diabetic patients can increase the density of myocardial blood vessels and thus reduce heart dysfunction caused by isoemia.
SIRT3 improves HG-induced ROS formation and apoptosis In addition, the specific knock-off of SIRT3 in endotential cells leads to an increase in phosphate oxide and a decrease in glycolysis, which in turn leads to angiogenesty and throosphageal dysfunction.
and apoptosis regulator (TIGAR) induced by TP53 is a new downstream target gene of tumor suppressor p53.
tigar is involved in a variety of biological processes, including glycolysis metabolism, apoptosis, cell cycles and cell death.
p53 accumulation in the failed heart has two effects, inducing cell cycle stagnation, resulting in proliferative cells stagnating in the G1 stage of the cell cycle, thereby inducing aging and inhibiting angiogenesia.
in hypoxia, p53 and its transcription target gene TIGAR were activated in myocardial cells, and the expression of p53 was also increased in myocardial cells.
p53 reduces capillary formation by inhibiting the hypoxia-induced factor-1 alpha in the hypertrophobic heart.
p53 in endoblast cells (EC) can reduce EC apoptosis and increase capillaries density.
the knock-on of TIGAR also showed a reduction in isohemia heart failure.
under HG conditions, TIGAR knock-out improved the metabolism of myocardial cells, and SIRT3 reduced diabetic cardiomyopathy by regulating p53 acetylation and TIGAR expression.
, SIRT3 may be the target of abnormal energy metabolism in diabetes.