title: Overexpression of SIRT1 in vascular smooth muscle cells attenuates angiotensin II-induced vascular remodeling and hypertension in mice.
abstract: Angiotensin II (AngII) induces the development of vascular hypertrophy and hypertension. We have shown previously that overexpression of class III deacetylase SIRT1 inhibits AngII-induced hypertrophy in vascular smooth muscle cells (VSMCs). However, the direct role of SIRT1 in VSMCs in response to AngII infusion in vivo remains unclear. Here, we found that the expression and activity of SIRT1 in mouse aortas was decreased significantly by AngII infusion. VSMC-specific SIRT1 transgene (SV-Tg) prevented the increase in systolic blood pressure (SBP) caused by AngII infusion without affecting heart function in mice. SIRT1 overexpression alleviated vascular remodeling in mouse thoracic and renal aortas induced by AngII infusion, and significantly inhibited reactive oxygen species (ROS) generation, vascular inflammation, and collagen synthesis in arterial walls. Reduced expression of transforming growth factor-β 1 (TGF-β1) was also observed in the aortas of AngII-infused SV-Tg mice. Moreover, SIRT1 overexpression decreased AngII-increased binding of nuclear factor-κB on its specific binding sites on TGF-β1 promoter. Taken together, these data demonstrate that SIRT1 overexpression in VSMCs reduces SBP and inhibits AngII-induced vascular remodeling in mice. The inhibition of vascular remodeling contributes, at least in part, to the antihypertensive effect of SIRT1.
  
  
  CONCLUSIONS
  SIRT1 is reduced in aortas of AngII-infused hypertensive mice. SIRT1 VSMC transgene alleviates AngII-increased systolic blood pressure. SIRT1 VSMC transgene attenuates AngII-induced vascular remodeling. VSMC SIRT1 overexpression inhibits remodeling-related pathological changes. VSMC SIRT1 overexpression reduces AngII-induced TGF-β1 expression.
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, No.5 Dong Dan San Tiao, Beijing, 100050, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Gao
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Xu
authors.forename: Jie
authors.initials: J
authors.lastname: Lu
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.forename: De-Long
authors.initials: DL
authors.lastname: Hao
authors.forename: Hou-Zao
authors.initials: HZ
authors.lastname: Chen
authors.forename: De-Pei
authors.initials: DP
authors.lastname: Liu
mesh_terms: D000804:Angiotensin II; D000818:Animals; D001011:Aorta / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D044127:Epigenesis, Genetic; D015870:Gene Expression; D006973:Hypertension / Q000139:chemically induced / Q000201:enzymology*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000201:enzymology; D032389:Myocytes, Smooth Muscle / Q000201:enzymology; D017382:Reactive Oxygen Species / Q000378:metabolism; D056564:Sirtuin 1 / Q000235:genetics* / Q000378:metabolism; D014657:Vasculitis / Q000139:chemically induced / Q000201:enzymology
chemical_list: D017382:Reactive Oxygen Species; D000804:Angiotensin II; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1