title: SRT1720, a SIRT1 specific activator, protected H2O2-induced senescent endothelium.
abstract: Silent information regulator 1 (SIRT1) plays a critical role in maintaining vascular homeostasis via modulating senescent-related signal pathway, however, the molecular mechanism remains modest clarified. The purpose of this study was to examine whether SIRT1 specific activator SRT1720 would exhibit pro-angiogenic and anti-aging properties in response to hydrogen peroxide (H2O2)-induced endothelial senescence, and determine the underlying mechanisms. We pre-treated senescent human umbilical vein endothelial cells (HUVECs) with SRT1720, senescence-associated beta-galactosidase activity, apoptosis, migration, tube formation, proliferation and angiogenic factors were quantitatively examined. The results revealed that pharmacologic activation of SIRT1 by SRT1720 rescued apoptotic HUVECs and upregulated angiogenic response through reinforcing the protein expressions of angiogenic and survival factors in vitro. Furthermore, we confirmed that the expressions of endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF) and phosphoryl-Akt were augmented in SRT1720-treated senescent HUVECs. In conclusion, our data indicated that SRT1720 could protect against endothelial senescence and maintain cell function via Akt/eNOS/VEGF axis.
authors: Department of Gerontology, Xinhua Hospital, Shanghai Jiaotong University School of MedicineKongjiang Road 1665, Shanghai 200092, China; Department of Vascular Surgery, Ren Ji Hospital, Shanghai Jiaotong University School of MedicineDongfang Road 1630, Shanghai 200127, China.
authors: Rui-Lin
authors: RL
authors: Li
authors: Department of Gerontology, Xinhua Hospital, Shanghai Jiaotong University School of MedicineKongjiang Road 1665, Shanghai 200092, China; Department of Vascular Surgery, Ren Ji Hospital, Shanghai Jiaotong University School of MedicineDongfang Road 1630, Shanghai 200127, China.
authors: Zhao-Yang
authors: ZY
authors: Lu
authors: Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University Huaihai Xi Road 241, Xuhui District, Shanghai 200030, China.
authors: Jing-Juan
authors: JJ
authors: Huang
authors: Department of Gerontology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine Kongjiang Road 1665, Shanghai 200092, China.
authors: Jia
authors: J
authors: Qi
authors: Department of Gerontology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine Kongjiang Road 1665, Shanghai 200092, China.
authors: An
authors: A
authors: Hu
authors: Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology Meilong Road 130, Shanghai 200237, China.
authors: Zhi-Xiao
authors: ZX
authors: Su
authors: Department of Vascular Surgery, Ren Ji Hospital, Shanghai Jiaotong University School of Medicine Dongfang Road 1630, Shanghai 200127, China.
authors: Lan
authors: L
authors: Zhang
authors: Department of Internal Medicine, University of Iowa Carve College of Medicine 2000 Medical Laboratories 25 South Grand Avenue, Iowa City, IA 52242, USA.
authors: Yue
authors: Y
authors: Li
authors: Department of Nephrology Zhongshan Hospital, Fudan University Fenglin Road 180, Shanghai 200032, China.
authors: Yi-Qin
authors: YQ
authors: Shi
authors: Department of Vascular Surgery, Ren Ji Hospital, Shanghai Jiaotong University School of Medicine Dongfang Road 1630, Shanghai 200127, China.
authors: Chang-Ning
authors: CN
authors: Hao
authors: Department of Gerontology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine Kongjiang Road 1665, Shanghai 200092, China.
authors: Jun-Li
authors: JL
authors: Duan
keywords: Endothelial cell senescence; SIRT1; VEGF; eNOS