title: Indole-3-carbinol protects against pressure overload induced cardiac remodeling via activating AMPK-α.
abstract: METHODS
  Indole-3-carbinol (I3C), a monomer component extracted from leaves and stems of cruciferous vegetables, has inhibitory effects on tumors, obesity, and liver fibrosis, but its effects on the development of cardiac remodeling remain completely unknown. We determined the effects of I3C on cardiac remodeling and heart function using an aortic banding (AB) mouse model.
  
  
  RESULTS
  Male 8- to10-wk-old wild-type and 5' adenosine monophosphate-activated protein kinase (AMPK)-α2 knockout mice fed with or without I3C were subjected to AB or a sham operation and were phenotyped, accordingly. I3C both prevented and reversed cardiac remodeling induced by AB, as assessed by heart weight/body weight, lung weight/body weight, and heart weight/tibia length ratios, echocardiographic and hemodynamic parameters, histological analysis, and gene expression of hypertrophic and fibrotic markers. The inhibitory effect of I3C on cardiac remodeling was mediated by AMPK-α and extracellular signal-regulated kinases 1/2 (ERK1/2) signaling. Moreover, AMPK-α2 gene deficiency completely blocked the inhibitory effects of I3C on cardiac remodeling, preventing the improvements in heart weight/body weight, lung weight/body weight, heart weight/tibia length, cardiac function, gene expression of hypertrophic and fibrotic markers, and phosphorylation of mammalian target of rapamycin and ERK1/2 signaling components.
  
  
  CONCLUSIONS
  I3C both prevents and reverses cardiac remodeling by activating AMPK-α signaling. I3C is a potential therapeutic drug for heart failure.
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Deng
authors.forename: Jing
authors.initials: J
authors.lastname: Zong
authors.forename: Zhouyan
authors.initials: Z
authors.lastname: Bian
authors.forename: Heng
authors.initials: H
authors.lastname: Zhou
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: Haipeng
authors.initials: H
authors.lastname: Guo
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Difei
authors.initials: D
authors.lastname: Shen
authors.forename: Hongliang
authors.initials: H
authors.lastname: Li
authors.forename: Qizhu
authors.initials: Q
authors.lastname: Tang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001835:Body Weight; D006332:Cardiomegaly / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control*; D005355:Fibrosis; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D007211:Indoles / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009929:Organ Size / Q000187:drug effects; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D011312:Pressure / Q000009:adverse effects*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D014675:Vegetables / Q000737:chemistry
chemical_list: D007211:Indoles; D010936:Plant Extracts; C016517:indole-3-carbinol; C546843:mTOR protein, mouse; C534978:Prkaa2 protein, mouse; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases
keywords: AMPK-α; Cardiac remodeling; Indole-3-carbinol