title: Attenuation of Low Ambient Temperature-Induced Myocardial Hypertrophy by Atorvastatin via Promoting Bcl-2 Expression.
abstract: OBJECTIVE
  It is well documented that myocardial hypertrophy is associated with low ambient temperature. Atorvastatin (Atv) has been shown to protect against atherosclerosis, cardiac fibrosis, ischemia/reperfusion injury, etc. In this study, we aim to determine whether atorvastatin is effective in the treatment of myocardial hypertrophy induced by cold exposure and to shed light on underlying mechanism.
  
  
  METHODS
  The mice aged 4-week were randomized to Control (Ctl) group (raised at room temperature), Cold group (raised at 3-5ºC) and Atv treatment group (raised at 3-5ºC followed by 10mg/kg/day Atv infusion). Echocardiography (ECG), HE, TUNEL and Masson's trichrome staining, and Transmission electronic microscopy were performed to analyze cardiac function, myocardial hypertrophy, cardiac fibrosis, apoptosis and cardiomyocyte ultrastructure, respectively. Western blot was carried out to determine the involvement of MAPK and apoptosis pathways.
  
  
  RESULTS
  Exposure of mice to low temperature induced myocardial hypertrophic growth characterized by the elevation of heart/body weight index and heart weight /tibia length index, compared with control mice. Atv treatment attenuated cardiac hypertrophy induced by cold exposure; Atv also attenuated the increase of cross-sectional area of cardiomyocytes and cardiac collagen content fraction in mice exposed to cold. ECG showed that the decline of cardiac functions including the elevated left ventricular systolic/diastolic internal dimension (LVIDs/d) and fractional shortening (FS) in mice with cold exposure was also inhibited by Atv treatment. Transmission electronic microscopy uncovered that Atv attenuated mitochondrial injury induced by cold exposure in mice. In addition, systolic blood pressure was gradually increased in mice exposed to cold temperature, and Atv treatment significantly inhibited the elevation of blood pressure in cold-treated mice. Mechanistically, mitogen-activated protein kinase (MAPK) signal was not altered in mice exposed to cold, and Atv did not affect MAPK signal in cold-treated mice. But Atv mitigated the reduction of Bcl-2/Bax level in heart of cold-treated mice.
  
  
  CONCLUSIONS
  Atv attenuated myocardial hypertrophy induced by cold exposure through inhibiting the downregulation of Bcl-2 in heart. It may provide a novel strategy for low temperature-induced myocardial hypertrophy treatment.
authors.forename: Jing
authors.initials: J
authors.lastname: Liang
authors.forename: Kun
authors.initials: K
authors.lastname: Yin
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Cao
authors.forename: Zhenbo
authors.initials: Z
authors.lastname: Han
authors.forename: Qi
authors.initials: Q
authors.lastname: Huang
authors.forename: Lai
authors.initials: L
authors.lastname: Zhang
authors.forename: Wenya
authors.initials: W
authors.lastname: Ma
authors.forename: Fengzhi
authors.initials: F
authors.lastname: Ding
authors.forename: Chongwei
authors.initials: C
authors.lastname: Bi
authors.forename: Dan
authors.initials: D
authors.lastname: Feng
authors.forename: Zhenwei
authors.initials: Z
authors.lastname: Pan
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D000069059:Atorvastatin / Q000494:pharmacology* / Q000627:therapeutic use; D001343:Autophagy / Q000187:drug effects; D001794:Blood Pressure; D006332:Cardiomegaly / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D003080:Cold Temperature; D015536:Down-Regulation / Q000187:drug effects; D004452:Echocardiography; D006352:Heart Ventricles / Q000000981:diagnostic imaging; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008297:Male; D051379:Mice; D046529:Microscopy, Electron, Transmission; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D000069059:Atorvastatin; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases
keywords: Atorvastatin; Bcl-2; Cardiac hypertrophy; Cold; Heart; p38