17beta-estradiol inhibits angiotensin II-induced cardiac myofibroblast differentiation.
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.
Wu
Meiling
M
Jiangsu Province Key Lab of Reproductive Medicine, Department of Pathophysiology, Nanjing Medical University, Nanjing, 210029, PR China.
Han
Mei
M
Li
Jing
J
Xu
Xuan
X
Li
Ting
T
Que
Lingli
L
Ha
Tuanzhu
T
Li
Chuanfu
C
Chen
Qi
Q
Li
Yuehua
Y
D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D009206:Myocardium / Q000166:cytology*; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D016328:NF-kappa B; D000804:Angiotensin II; D004958:Estradiol; D048051:p38 Mitogen-Activated Protein Kinases