title: Endothelin-1-Induced Cell Hypertrophy in Cardiomyocytes is Improved by Fenofibrate: Possible Roles of Adiponectin.
abstract: OBJECTIVE
  Previous studies demonstrated that endothelin-1 (ET-1) can significantly increase the cell size and stimulate adiponectin expression in cultured human cardiomyocytes (HCM). The aim of the present study was to investigate the effects of fenofibrate, a peroxisome proliferator-activated receptor-α (PPARα) activator, on cell hypertrophy and adiponectin expression in vitro and in a rat model of daunorubicin-induced cardiomyopathy.
  
  
  METHODS
  The cultured human cardiomyocytes (HCM) were stimulated with or without ET-1. The cell size and the protein expressions of PPARα and adiponectin were tested by confocal Immunofluorescence study and Western blot, respectively. To study the effects of PPARα activation on ET-1-induced cell hypertrophy and adiponectin protein synthesis, HCM were pretreated with fenofibrate or small interfering RNA (siRNA) of PPARα. Echocardiographic parameters were measured and immunohistochemistry study of myocardial adiponectin expression was conducted in the in vivo study.
  
  
  RESULTS
  ET-1 significantly increased the cell size, dose-dependently suppressed the expression of PPARα, and enhanced the expression of adiponectin; whereas, such an increase of cell size and enhancement of adiponectin expression were inhibited by the pre-treatment with fenofibrate. Addition of siRNA of PPARα abolished the effects of fenofibrate. Moreover, we found that fenofibrate treatment can significantly improve the left ventricular function and reverse the myocardial expression of adiponectin.
  
  
  CONCLUSIONS
  Our study shows that fenofibrate may protect against ET-1-induced cardiomyocyte hypertrophy and enhanced adiponectin expression through modulation of PPARα expression in vitro and limitation of daunorubicin cardiotoxicity in vivo, suggesting a novel mechanistic insight into the role of PPARα and adiponectin in cardiac hypertrophy and heart failure.
authors.affiliation: Division of Cardiology, Cheng-Hsin General Hospital.|Institute of Clinical Medicine, National Yang-Ming University.
authors.forename: Hsu-Lung
authors.initials: HL
authors.lastname: Jen
authors.affiliation: Division of Cardiology, Cheng-Hsin General Hospital.|Faculty of Medicine, National Yang-Ming University.|Cardiovascular Research Centre, School of Medicine, National Yang-Ming University.
authors.forename: Wei-Hsian
authors.initials: WH
authors.lastname: Yin
authors.affiliation: Department of Medical Research and Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital.|Institute of Pharmacology, National Yang-Ming University.|Cardiovascular Research Centre, School of Medicine, National Yang-Ming University.
authors.forename: Jaw-Wen
authors.initials: JW
authors.lastname: Chen
authors.affiliation: Department of Medical Research and Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital.|Institute of Clinical Medicine, National Yang-Ming University.|Cardiovascular Research Centre, School of Medicine, National Yang-Ming University.
authors.forename: Shing-Jong
authors.initials: SJ
authors.lastname: Lin
mesh_terms: D052242:Adiponectin / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D006332:Cardiomegaly / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D019332:Endothelin-1 / Q000633:toxicity*; D011345:Fenofibrate / Q000494:pharmacology*; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D047493:PPAR alpha / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D019332:Endothelin-1; D000960:Hypolipidemic Agents; D047493:PPAR alpha; D011345:Fenofibrate
keywords: Adiponectin; Cardiomyocyte hypertrophy; Endothelin-1; Fenofibrate; Peroxisome proliferator-activated receptor