17β-estradiol inhibits human umbilical vascular endothelial cell senescence by regulating autophagy via p53.

Abstract

Vascular endothelial cell (VEC) senescence is an initiating factor in numerous cardiovascular diseases. Recent studies showed that 17β-estradiol (17β-E2), an estrogen with numerous biological activities such as inhibition of atherosclerosis, protects VECs from senescence. However, the effects of 17β-E2 on human umbilical VECs (HUVECs) remain unknown. This study investigated the anti-senescent effect of 17β-E2 on HUVECs and explored the underlying mechanism with respect to autophagy and p53 activity. First, rapamycin and 3-methyladenine were used to clarify the relationship between autophagy and senescence in HUVECs, and an inverse relationship was demonstrated. Next, the effect of 17β-E2 on H2O2-induced senescence of HUVECs was examined. Increased autophagy induced by 17β-E2 inhibited H2O2-induced senescence of HUVECs, increased cell viability, and maintained HUVEC morphology. 17β-E2 pre-treatment also decreased cell cycle arrest, decreased the dephosphorylation of Rb, decreased the production of ET-1, and increased the production of NO. Most importantly, 17β-E2 pre-treatment increased autophagy by activating p53 and its downstream effector p53-upregulated modulator of apoptosis (PUMA). Overall, our data indicate the critical role of autophagy in the anti-senescent effect of 17β-E2 on HUVECs.