All- trans retinoic acid inhibited angiotensin II-induced increase in cell growth and collagen secretion of neonatal cardiac fibroblasts

Aim: To determine whether all-trans retinoic acid (at RA) 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-β₁ (TGF-β₁) by the CF. Results: at RA (1×10^-7 to 1×10^-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 AT1 receptor antagonist losartan (1×10^-6 mol/L), but not by AT2 receptor antagonist PD123319 (up to 1×10^-6 mol/L). Exposure of CF to at RA (1×10^-5 mol/L) attenuated the Ang II-induced increase in the secretion of collagen types I and III (P<0.05). a t RA (1×10^-5 mol/L) also blocked the Ang IIinduced increase in the expression of TGF-β₁. Conclusion: at RA inhibits the Ang II-induced increase in cell growth and collagen secretion of neonatal rat CF. The effect of at RA is possibly mediated by lowering the TGF-β₁ level. These observations support the notion that at RA is a potential candidate for the prevention and therapy of cardiac remodeling.