Simvastatin attenuates hypertrophic responses induced by cardiotrophin-1 via JAK-STAT pathway in cultured cardiomyocytes

L J Wu, L Y Zhao, Q S Zheng, F J Shang, X M Wang, L F Wang, B Lang

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Cardiotrophin-1 (CT-1) is a cytokine involved in the growth and survival of cardiac cells via activation of the Janus activated kinase/signal transducer activator of transcription (JAK/STAT). Statins, 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, have effects that extend beyond cholesterol reduction and inhibit vascular smooth muscle cell (VSMC) proliferation and cardiac hypertrophy. However, whether stains also can inhibitin vitromyocardial hypertrophy or not still remains elusive. The purpose of this study was to explore the effects of simvastatin on the hypertrophy of cultured rat cardiomyocytes induced by CT-1 and to investigate whether this effect was mediated via JAK-STAT signaling pathway.Methods and Results: Primary cardiomyocytes from 2-day-old (P2) rats were cultured, stimulated with CT-1, and treated with various concentration of simvastatin. Incorporation of [H-3] leucine, reverse transcription-polymerase chain reaction and western blotting techniques were used to investigate cardiacmyocyte size, ANP mRNA and JAK-STAT protein expression. Simvastatin was proved, in a dose-independent manner, to decrease cardiacmyocytes size as well as protein synthesis, and inhibit ANP mRNA synthesis and JAK-STAT protein expression induced by CT-1 in cardiacmyocytes.Conclusion: These results suggest that simvastatin can ameliorate cardiacmyocytes hypertrophyin vitrovia JAK-STAT signaling pathways. The present study provides a novel understanding and alternative therapeutic strategy for cardiac hypertrophy.

Original languageEnglish
Pages (from-to)65-71
Number of pages7
JournalMolecular & Cellular Biochemistry
Volume284
Issue number1-2
DOIs
Publication statusPublished - Mar 2006

Keywords

  • cardiotrophin-1
  • cardiacmyocyte
  • hypertrophy
  • JAK-STAT
  • simvastatin
  • LEFT-VENTRICULAR HYPERTROPHY
  • CARDIAC MYOCYTE HYPERTROPHY
  • COA REDUCTASE INHIBITORS
  • SIGNALING PATHWAYS
  • HEART-FAILURE
  • PROGNOSTIC IMPLICATIONS
  • MYOCARDIAL-INFARCTION
  • EXPRESSION
  • ACTIVATION
  • FRAMINGHAM

Cite this