SIRT2 plays a significant role in maintaining the survival and energy metabolism of PIEC endothelial cells.

SIRT2, a member of the sirtuin (SIRT1-7) family, is a tubulin deacetylase. It has been reported that SIRT2 mediates cellular stress responses and is highly expressed in vascular endothelial cells, while its roles in cell survival and energy metabolism of endothelial cells remain unknown. In the current study, we tested our hypothesis that SIRT2 plays an important role in the cell survival and energy metabolism of endothelial cells, using a porcine vascular endothelial cell line (PIEC) as a cellular model. Our study showed that both SIRT2 inhibitor AGK2 and SIRT2 siRNA led to a significant reduction of the cell survival of PIEC cells. Our FACS-based Annexin V/7-AAD assay and Hoechst staining showed that both SIRT2 inhibitor and SIRT2 siRNA led to a significant increase in apoptosis and necrosis of the cells. Moreover, the SIRT2 inhibition led to both mitochondrial depolarization and decreases in the intracellular ATP level of the cells. Collectively, our study has provided the first evidence suggesting that SIRT2 plays a significant role in maintaining both the survival and the mitochondrial membrane potential of PIEC cells, which may account for the major effects of SIRT2 on the intracellular ATP level of the cells.