• Shicong Song, Saizhu Wu, Yuyan Wang, Zhiwei Wang, Changxiong Ye, Rui Song, Dongqing Song, and Yunjun Ruan.
• Department of Gerontology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
• Exp. Gerontol. 2018 Dec 1; 114: 57-66.

AbstractVascular 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.Copyright © 2018 Elsevier Inc. All rights reserved.

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