17beta-estradiol inhibits angiotensin II-induced cardiac myofibroblast differentiation

Eur J Pharmacol. 2009 Aug 15;616(1-3):155-9. doi: 10.1016/j.ejphar.2009.05.016. Epub 2009 May 24.

Abstract

Cardiac fibroblasts play an important role in myocardial remodeling by proliferating, differentiating, and secreting extracellular matrix proteins. Estrogen has been reported to have a number of cardioprotective properties. However, it is unclear whether estrogen affects cardiac fibroblast differentiation. The purpose of the present study was to investigate the effect of estrogen on angiotensin II-induced cardiac fibroblast proliferation and differentiation. Cardiac fibroblasts were stimulated with angiotensin II (1 microM) in the presence or absence of 17beta-estradiol (100 nM). Pretreatment of cardiac fibroblasts with 17beta-estradiol significantly inhibited angiotensin II-induced cardiac fibroblast proliferation and differentiation (indicated by a reduction in alpha-smooth muscle actin (alpha-SMA) expression) by 25% and 20%. Pretreatment of 17beta-estradiol significantly reduced angiotensin II-increased levels of phospho-p38 mitogen-activated protein kinase (MAPK) by 40% and nuclear factor-kappaB (NF-kappaB) binding activity in cardiac fibroblasts by 55%. Our data suggests estrogen could have an anti-fibrotic effect through limiting cardiac fibroblast proliferation and differentiation, which are the critical steps in the pathogenesis of cardiac fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / antagonists & inhibitors*
  • Angiotensin II / pharmacology*
  • Animals
  • Cell Differentiation / drug effects*
  • Cell Proliferation / drug effects
  • Estradiol / pharmacology*
  • Fibroblasts / cytology*
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • In Vitro Techniques
  • Myocardium / cytology*
  • NF-kappa B / metabolism
  • Phosphorylation / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • NF-kappa B
  • Angiotensin II
  • Estradiol
  • p38 Mitogen-Activated Protein Kinases