All-trans retinoic acid inhibited angiotensin II-induced increase in cell growth and collagen secretion of neonatal cardiac fibroblasts.
OBJECTIVE
To determine whether all-trans retinoic acid (atRA) acts to modulate angiotensin II (Ang II)-induced cardiac fibroblast cell growth and collagen secretion.


METHODS
Cultured neonatal rat cardiac fibroblasts (CF) were used in the experiment. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to detect cell growth of the CF; and immunocytochemistry and Western blotting were used to measure the production and secretion of collagen and the expression of transforming growth factor-beta1 (TGF-beta1) by the CF.


RESULTS
atRA (10(-7) to 10(-5) mol/L) inhibited the Ang II-induced increase in cell growth of CF (P<0.05). Ang II stimulated the secretion of collagen types I and III by the CF. This effect was blocked by AT(1) receptor antagonist losartan (10(-6) mol/L), but not by AT2 receptor antagonist PD123319 (up to 10(-6) mol/L). Exposure of CF to atRA (10(-5) mol/L) attenuated the Ang II-induced increase in the secretion of collagen types I and III (P<0.05). atRA (10(-5) mol/L) also blocked the Ang II-induced increase in the expression of TGF-beta1.


CONCLUSIONS
atRA inhibits the Ang II-induced increase in cell growth and collagen secretion of neonatal rat CF. The effect of atRA is possibly mediated by lowering the TGF-beta1 level. These observations support the notion that atRA is a potential candidate for the prevention and therapy of cardiac remodeling.
He
Yan
Y
Department of Physiology and Pathophysiology, Fudan University Shanghai Medical College, Shanghai 200032, China.
Huang
Ying
Y
Zhou
Li
L
Lu
Li-Min
LM
Zhu
Yi-Chun
YC
Yao
Tai
T
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D049109:Cell Proliferation / Q000187:drug effects*; D024042:Collagen Type I / Q000378:metabolism*; D024061:Collagen Type III / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D014212:Tretinoin / Q000494:pharmacology*
D024042:Collagen Type I; D024061:Collagen Type III; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D000804:Angiotensin II; D014212:Tretinoin