Mechanism of the inhibitory effect of atorvastatin on endoglin expression induced by transforming growth factor-1 in cultured cardiac fibroblasts

Kou Gi Shyu, Bao Wei Wang, Wei Jan Chen, Peiliang Kuan, Chi Ren Hung

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

AimsTransforming growth factor-1 (TGF-1) and endoglin play a causal role in promoting cardiac fibrosis. Atorvastatin has been shown to have an inhibitory effect on cardiac fibroblasts in vitro. However, the effects of statins on TGF-1 and endoglin are poorly understood. We therefore sought to investigate the molecular mechanisms of atorvastatin on endoglin expression after TGF-1 stimulation in cardiac fibroblasts.Methods and resultsCultured cardiac fibroblasts were obtained from adult male Sprague-Dawley rat hearts. TGF-1 stimulation increased endoglin and collagen I expression and atorvastatin inhibited the induction of endoglin and collagen I by TGF-1. Phosphatidylinositol-3 kinase (PI-3) and Akt inhibitors (wortmannin and Akt inhibitor X) completely attenuated the endoglin protein expression induced by TGF-1. TGF-1 induced phosphorylation of PI-3 kinase and Akt, while atorvastatin and wortmannin and Akt inhibitor X inhibited the phosphorylation of PI-3 kinase and Akt induced by TGF-1. The gel shift and promoter activity assay showed that TGF-1 increased Smad3/4-binding activity and endoglin promoter activity, while wortmannin and atorvastatin inhibited the Smad3/4-binding activity and endoglin promoter activity induced by TGF-1. TGF-1 increased collagen I protein expression, while endoglin siRNA attenuated collagen I protein expression induced by TGF-1. Atorvastatin decreased left ventricular TGF-1, endoglin, and collagen I protein expression and fibrotic area in a rat model of volume overload heart failure.ConclusionAtorvastatin inhibits endoglin expression through the inhibition of PI-3 kinase, Akt, and Smad3 phosphorylation, and reduced Smad3/4 binding activity and endoglin promoter activity in cardiac fibroblasts.

Original languageEnglish
Pages (from-to)219-226
Number of pages8
JournalEuropean Journal of Heart Failure
Volume12
Issue number3
DOIs
Publication statusPublished - Mar 2010

Keywords

  • Endoglin
  • Fibroblast
  • Fibrosis
  • Statin
  • Transforming growth factor-β1

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Mechanism of the inhibitory effect of atorvastatin on endoglin expression induced by transforming growth factor-1 in cultured cardiac fibroblasts'. Together they form a unique fingerprint.

  • Cite this