Aim: Vascular endothelial cell senescence is a leading cause of age-associated diseases and cardiovascular diseases. Interventions and therapies targeting endothelial cell senescence and dysfunction would have important clinical implications. This study was aimed to evaluate the effect of 10 resveratrol analogues, including pterostilbene (Pts) and its derivatives, against endothelial senescence and dysfunction.
Methods and Results: All the tested compounds at the concentrations from 10-9 M to 10-6 M did not show cytotoxicity in endothelial cells. Among the 10 resveratrol analogues, Pts and Pts nicotinate attenuated the expression of senescence-associated β-galactosidase, downregulated p21 and p53, and increased the production of NO in both angiotensin II and H2O2-induced endothelial senescence models. In addition, Pts and Pts nicotinate elicited endothelium-dependent relaxations. Pts and Pts nicotinate did not alter Sirtuin 1 (SIRT1) expression but enhanced its activity. Both Pts and Pts nicotinate have high binding activities with SIRT1. Inhibition of SIRT1 by sirtinol reversed the anti-senescent effects of Pts and Pts nicotinate.
Conclusions: This study suggests that the Pts and Pts nicotinate ameliorated vascular endothelial senescence and elicited endothelium-dependent relaxations via activation of SIRT1. These two compounds maybe potential drugs for the treatment of cardiovascular diseases related to endothelial senescence and dysfunction.
Apelin/APJ axis improves angiotensin II-induced endothelial cell senescence through AMPK/SIRT1 signaling pathway
