title: SIRT1 acts as a modulator of neointima formation following vascular injury in mice.
abstract: BACKGROUND
  Vascular smooth muscle cell (VSMC) proliferation and migration are crucial events involved in the pathophysiology of vascular diseases. Sirtuin 1 (SIRT1), a class III histone deacetylase (HDAC), has been reported to have the function of antiatherosclerosis, but its role in neointima formation remains unknown.
  
  
  OBJECTIVE
  The present study was designed to investigate the role of SIRT1 in the regulation of neointima formation and to elucidate the underlying mechanisms.
  
  
  RESULTS
  A decrease in SIRT1 expression was observed following carotid artery ligation. smooth muscle cell (SMC)-specific human SIRT1 transgenic (Tg) mice were generated. SIRT1 overexpression substantially inhibited neointima formation after carotid artery ligation or carotid artery wire injury. In the intima of injured carotid arteries, VSMC proliferation (proliferating cell nuclear antigen (PCNA)-positive cells) was significantly reduced. SIRT1 overexpression markedly inhibited VSMC proliferation and migration and induced cell cycle arrest at G1/S transition in vitro. Accordingly, SIRT1 overexpression decreased the induction of cyclin D1 and matrix metalloproteinase-9 (MMP-9) expression by treatment with serum and TNF-α, respectively, whereas RNAi knockdown of SIRT1 resulted in the opposite effect. Decreased cyclin D1 and MMP-9 expression/activity were also observed in injured carotid arteries from SMC-SIRT1 Tg mice. Furthermore, 2 targets of SIRT1, c-Fos and c-Jun, were involved in the downregulation of cyclin D1 and MMP-9 expression.
  
  
  CONCLUSIONS
  Our findings demonstrate the inhibitory effect of SIRT1 on the VSMC proliferation and migration that underlie neointima formation and implicate SIRT1 as a potential target for intervention in vascular diseases.
authors.affiliation: National Laboratory of Medical Molecular Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, No 5 Dong Dan San Tiao, Beijing 100005, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Hui-Na
authors.initials: HN
authors.lastname: Zhang
authors.forename: Hou-Zao
authors.initials: HZ
authors.lastname: Chen
authors.forename: Peng
authors.initials: P
authors.lastname: Gao
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Zhu
authors.forename: Hong-Liang
authors.initials: HL
authors.lastname: Li
authors.forename: Xiang
authors.initials: X
authors.lastname: Lv
authors.forename: Qing-Jun
authors.initials: QJ
authors.lastname: Zhang
authors.forename: Ran
authors.initials: R
authors.lastname: Zhang
authors.forename: Zhao
authors.initials: Z
authors.lastname: Wang
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: She
authors.forename: Ran
authors.initials: R
authors.lastname: Zhang
authors.forename: Yu-Sheng
authors.initials: YS
authors.lastname: Wei
authors.forename: Guan-Hua
authors.initials: GH
authors.lastname: Du
authors.forename: De-Pei
authors.initials: DP
authors.lastname: Liu
authors.forename: Chih-Chuan
authors.initials: CC
authors.lastname: Liang
mesh_terms: D000818:Animals; D020212:Carotid Artery Injuries / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D006801:Humans; D008026:Ligation; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D058426:Neointima / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D056564:Sirtuin 1 / Q000096:biosynthesis / Q000502:physiology*
chemical_list: C447939:SIRT1 protein, human; D056564:Sirtuin 1