Endothelin-1-induced cell hypertrophy in cardiomyocytes is improved by fenofibrate: Possible roles of adiponectin

Hsu Lung Jen, Wei Hsian Yin, Jaw Wen Chen, Shing Jong Lin

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

Aim: 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 Immunofluo-rescence 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 immu-nohistochemistry 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.

Original languageEnglish
Pages (from-to)508-517
Number of pages10
JournalJournal of Atherosclerosis and Thrombosis
Volume24
Issue number5
DOIs
Publication statusPublished - 2017
Externally publishedYes

Keywords

  • Adiponectin
  • Cardiomyocyte hypertrophy
  • Endothelin-1
  • Fenofibrate
  • Peroxisome proliferator-activated receptor

ASJC Scopus subject areas

  • Internal Medicine
  • Cardiology and Cardiovascular Medicine
  • Biochemistry, medical

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