title: SIRT1 functions as an important regulator of estrogen-mediated cardiomyocyte protection in angiotensin II-induced heart hypertrophy.
abstract: BACKGROUND
  Sirtuin 1 (SIRT1) is a member of the sirtuin family, which could activate cell survival machinery and has been shown to be protective in regulation of heart function. Here, we determined the mechanism by which SIRT1 regulates Angiotensin II- (AngII-) induced cardiac hypertrophy and injury in vivo and in vitro.
  
  
  METHODS
  We analyzed SIRT1 expression in the hearts of control and AngII-induced mouse hypertrophy. Female C57BL/6 mice were ovariectomized and pretreated with 17β-estradiol to measure SIRT1 expression. Protein synthesis, cardiomyocyte surface area analysis, qRT-PCR, TUNEL staining, and Western blot were performed on AngII-induced mouse heart hypertrophy samples and cultured neonatal rat ventricular myocytes (NRVMs) to investigate the function of SIRT1.
  
  
  RESULTS
  SIRT1 expression was slightly upregulated in AngII-induced mouse heart hypertrophy in vivo and in vitro, accompanied by elevated cardiomyocyte apoptosis. SIRT1 overexpression relieves AngII-induced cardiomyocyte hypertrophy and apoptosis. 17β-Estradiol was able to protect cardiomyocytes from AngII-induced injury with a profound upregulation of SIRT1 and activation of AMPK. Moreover, estrogen receptor inhibitor ICI 182,780 and SIRT1 inhibitor niacinamide could block SIRT1's protective effect.
  
  
  CONCLUSIONS
  These results indicate that SIRT1 functions as an important regulator of estrogen-mediated cardiomyocyte protection during AngII-induced heart hypertrophy and injury.
authors.affiliation: The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, Beijing 100730, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Shen
authors.affiliation: The Second Hospital of Shanxi Medical University, Taiyuan 030001, China ; Department of Cardiology, The General Hospital of Jincheng Anthracite Mining Group Co. Ltd., Jincheng 048006, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Ding
authors.affiliation: Capital Medical University Affiliated Beijing Anzhen Hospital, Beijing 100029, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Ruan
authors.affiliation: The Second Hospital of Shanxi Medical University, Taiyuan 030001, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Qin
authors.affiliation: The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, Beijing 100730, China.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Lin
authors.affiliation: College of Life Sciences, Beijing Normal University, Beijing 100875, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Xi
authors.affiliation: The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, Beijing 100730, China.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Lu
authors.affiliation: The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, Beijing 100730, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Dou
authors.affiliation: The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, Beijing 100730, China ; Capital Medical University Affiliated Beijing Anzhen Hospital, Beijing 100029, China.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, Beijing 100730, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Cao
authors.affiliation: The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, Beijing 100730, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Man
authors.affiliation: The Second Hospital of Shanxi Medical University, Taiyuan 030001, China.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Bian
authors.affiliation: The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, Beijing 100730, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Shanxi Medical University, Taiyuan, Shanxi 030001, China.
authors.forename: Chuanshi
authors.initials: C
authors.lastname: Xiao
authors.affiliation: The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, Beijing 100730, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced* / Q000378:metabolism*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000096:biosynthesis*
chemical_list: D000804:Angiotensin II; D004958:Estradiol; D056564:Sirtuin 1