SIRT3 protects endothelial cells from high glucose-induced cytotoxicity.

Diabetes is a frequent and increasing public health problem with a large economic burden in modern society. Endothelial cells dysfunction was involved in the development of diabetes-associated diseases. Sirtuins are a conserved family of NAD-dependent deacetylases. However, the role of sirtuins in diabetes-associated endothelial cell dysfunction was relatively unknown. In this study, we focus on the intrinsic link between SIRT3, a mitochondrial sirtuin, and high glucose-induced endothelial cells dysfunction. We showed that loss of SIRT3 expression was associated with decreased viability in endothelial cells from diabetes patients. Knockdown of SIRT3 decreased viability of endothelia cells exposed to high glucose condition. Further, mechanistic study showed that SIRT3 repression results in SOD2 acetylation, leading to SOD2 inactivation, which enhanced high glucose-induced oxidative stress in endothelial cells. Our data suggested that SIRT3 protects endothelial cells from high glucose-induced cytotoxicity. Our findings are considered a significant step toward a better understanding of diabetes-associated vascular diseases.