Silent information regulator 1 (SIRT1) plays a critical role in maintaining vascular homeostasis via modulating senescent-related signal pathway, however, the molecular mechanism remains modest clarified. The purpose of this study was to examine whether SIRT1 specific activator SRT1720 would exhibit pro-angiogenic and anti-aging properties in response to hydrogen peroxide (H2O2)-induced endothelial senescence, and determine the underlying mechanisms. We pre-treated senescent human umbilical vein endothelial cells (HUVECs) with SRT1720, senescence-associated beta-galactosidase activity, apoptosis, migration, tube formation, proliferation and angiogenic factors were quantitatively examined. The results revealed that pharmacologic activation of SIRT1 by SRT1720 rescued apoptotic HUVECs and upregulated angiogenic response through reinforcing the protein expressions of angiogenic and survival factors in vitro. Furthermore, we confirmed that the expressions of endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF) and phosphoryl-Akt were augmented in SRT1720-treated senescent HUVECs. In conclusion, our data indicated that SRT1720 could protect against endothelial senescence and maintain cell function via Akt/eNOS/VEGF axis.
Keywords: Endothelial cell senescence; SIRT1; VEGF; eNOS.