title: SIRT1-mediated ERβ suppression in the endothelium contributes to vascular aging.
abstract: SIRT1 has many important molecular functions in aging, and the estrogen receptors (ERs) have a vasculoprotective effect, although the detailed mechanism for the roles of SIRT1 and ERs in vascular aging remains unclear. We found that ERβ expression in the endothelium was reduced in aging mice, and the expression of ERα and SIRT1 did not change, while SIRT1 activity declined. Further investigation showed that the ERβ expression was regulated by SIRT1 through complexes of SIRT1-PPARγ/RXR-p300 that bind to a PPRE (PPAR response element) site on the ERβ promoter, and the declined SIRT1 function in aging mice was due to compromised phosphorylation at S154. A single-mutant SIRT1-C152(D) restored the reduced ERβ 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 ERβ or SIRT1-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 SIRT1-mediated ERβ suppression in the endothelium contributes to vascular aging, and the modulation of SIRT1 phosphorylation through a single-mutant SIRT1-C152(D) restores this effect.
authors.affiliation: School of Public Health, Guangdong Medical College, Dongguan, 523808, China.
authors.forename: Danli
authors.initials: D
authors.lastname: Kong
authors.affiliation: Tongji Wenchang Hospital, Huazhong University of Science and Technology, Wenchang, 571321, China.|Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhan
authors.affiliation: Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Zhaoyu
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Ding
authors.affiliation: Tongji Wenchang Hospital, Huazhong University of Science and Technology, Wenchang, 571321, China.|Inner Mongolia University for the Nationalities, #1742 Huolinhe Str. Tongliao, Inner Mongolia, 028000, China.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: School of Public Health, Guangdong Medical College, Dongguan, 523808, China.
authors.forename: Haibing
authors.initials: H
authors.lastname: Yu
authors.affiliation: Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Laxi
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Public Health, Guangdong Medical College, Dongguan, 523808, China.
authors.forename: Huawen
authors.initials: H
authors.lastname: Li
authors.affiliation: Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Aiyue
authors.initials: A
authors.lastname: Luo
authors.affiliation: Inner Mongolia University for the Nationalities, #1742 Huolinhe Str. Tongliao, Inner Mongolia, 028000, China.
authors.forename: Dongwei
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Guangzhou Biomedical Research and Development Center, Jinan University, Guangzhou, 510632, China.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Shixuan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Personalized Treatment Research Center, The Third Hospital of Wuhan, Wuhan, 430060, China.
authors.forename: Zhefan
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Hematology, Peking University ShenZhen Hospital, ShenZhen, 518036, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Personalized Treatment Research Center, The Third Hospital of Wuhan, Wuhan, 430060, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Huang
authors.affiliation: School of Public Health, Guangdong Medical College, Dongguan, 523808, China.|Tongji Wenchang Hospital, Huazhong University of Science and Technology, Wenchang, 571321, China.
authors.forename: Paul
authors.initials: P
authors.lastname: Yao
authors.affiliation: School of Public Health, Guangdong Medical College, Dongguan, 523808, China.
authors.forename: Yuanling
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Tongji Wenchang Hospital, Huazhong University of Science and Technology, Wenchang, 571321, China.
authors.forename: Zhengxiang
authors.initials: Z
authors.lastname: Liu
keywords: estrogen receptor; fatty acid metabolism; mitochondria; oxidative stress; vascular aging