Open AccessSIRT1‐mediated ERβ suppression in the endothelium contributes to vascular aging
Author(s) -
Kong Danli,
Zhan Ying,
Liu Zhaoyu,
Ding Ting,
Li Min,
Yu Haibing,
Zhang Laxi,
Li Huawen,
Luo Aiyue,
Zhang Dongwei,
Wang Yifei,
Wang Shixuan,
Zhang Zhefan,
Zhang Hongyu,
Huang Xiaodong,
Yao Paul,
Ding Yuanling,
Liu Zhengxiang
Publication year - 2016
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12515
Subject(s) - endothelium , biology , endocrinology , medicine , phosphorylation , receptor , estrogen receptor , microbiology and biotechnology , sirtuin 1 , biochemistry , downregulation and upregulation , gene , genetics , cancer , breast cancer
Summary SIRT 1 has many important molecular functions in aging, and the estrogen receptors ( ER s) have a vasculoprotective effect, although the detailed mechanism for the roles of SIRT 1 and ER s in vascular aging remains unclear. We found that ER β expression in the endothelium was reduced in aging mice, and the expression of ER α and SIRT 1 did not change, while SIRT 1 activity declined. Further investigation showed that the ER β expression was regulated by SIRT 1 through complexes of SIRT 1‐ PPAR γ/ RXR ‐p300 that bind to a PPRE ( PPAR response element) site on the ER β promoter, and the declined SIRT 1 function in aging mice was due to compromised phosphorylation at S154. A single‐mutant SIRT 1‐C152(D) restored the reduced ER β expression in the endothelium with minimized reactive oxygen species generation and DNA damage and increased mitochondrial function and fatty acid metabolism. In high‐fat diet aging mice, the endothelium‐specific delivery of ER β or SIRT 1‐C152(D) on the vascular wall reduced the circulating lipids with ameliorated vascular damage, including the restored vessel tension and blood pressure. We conclude that SIRT 1‐mediated ER β suppression in the endothelium contributes to vascular aging, and the modulation of SIRT 1 phosphorylation through a single‐mutant SIRT 1‐C152(D) restores this effect.