Soluble transforming growth factor-β1 receptor II might inhibit transforming growth factor-β-induced myofibroblast differentiation and improve ischemic cardiac function after myocardial infarction in rats

Objective Cardiac fibroblasts (CFs) regulate myocardial fibrosis and remodeling through proliferation and differentiation. Transforming growth factor-beta 1 (TGF-beta 1) plays a critical role in the development of myocardial fibrosis after myocardial infarction (MI). The aim of this study was to investigate the effects of inhibiting TGF-beta 1 action on myofibroblast differentiation and cardiac function after MI. Methods CFs were cultured and treated, respectively with PBS, TGF-beta 1, soluble TGF-beta 1 receptor II (sT beta RII), and TGF-beta 1 plus sT beta RII. Proliferation CFs were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Myofibroblast differentiation was examined by alpha-smooth muscle actin immunostaining. Expression of P-Smad2 and Smad2/3 was determined by immunostaining and western blot analysis. Four days after ligation of left anterior descending coronary artery, sT beta RII was injected into injured heart. Two weeks after sT beta RII administration, myofibroblast differentiation was measured with alpha-smooth muscle actin immunostaining. Four weeks after sT beta RII administration, cardiac function was evaluated by hemodynamic measurements. Weight parameters, infarct size, and collagen fiber were detected with an earlier experimental method. Results Compared with TGF-beta 1, TGF-beta 1 plus sT beta RII significantly decreased cell proliferation, myofibroblast differentiation, and expression of P-Smad2 in CFs (P<0.05). Two weeks after sT beta RII administration, myofibroblast differentiation in MI rats treated with sT beta RII was reduced compared with MI group (P<0.05). Four weeks after sT beta RII administration, MI rats that received sT beta RII showed significantly higher cardiac function and lower in weight parameters, infarct size, and collagen fiber than that of MI group (P<0.05). Conclusion sT beta RII could inhibit TGF-beta 1-induced myofibroblast differentiation, alleviate myocardial fibrosis and remodeling, and improve ischemic cardiac function after MI. Coron Artery Dis 21:369-377 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.