Concurrent vitamin D supplementation and exercise training improve cardiac fibrosis via TGF-β/Smad signaling in myocardial infarction model of rats.

Abstract

Although the role of vitamin D in various types of disorders such as cancer and diabetes has been well recognized, its relation to cardiovascular diseases still remains equivocal. The present study aims to investigate the interactive effects of aerobic-resistance training (ART) and vitamin D3 (VD3) on both cardiac fibrosis and heart functions considering TGF-β1/Smad2, 3 (transforming growth factor-β1/mothers against decapentaplegic homolog 2/3) signaling in the myocardial infarction (MI) model of rats. Fifty-six male Wistar rats were divided into 2 groups of sham (n = 8), and MI (n = 48). Then, MI rats were divided into six groups of VD3, ART, VD3+ART, Veh, Veh+ART, and sedentary MI. The animals received the related treatments for 8weeks, and then their functional exercise capacity (FEC) and strength gain (SG) were estimated through exercise tests. Ejection fraction (EF%) and fractional shortening (FS%) and serum level of VD3 were measured by echocardiography and ELISA, respectively. Cardiac expressions of TGF-β1, Smad2/3, and collagen I/III were assessed by western blotting and fibrosis by Masson's trichrome staining. The highest EF, parallel with the lowest expression of cardiac TGF-β1, Smad2/3, collagen I, and collagen III were observed in MI + VD3 (P = 0.021), MI + ART (P = 0.001), and MI + VD3 + ART (P < 0.001). Furthermore, similar to FS, the highest FEC and SG were related to the groups of MI + VD3 + ART and MI + ART compared to the MI group. In conclusion, our data indicate that concurrent vitamin D supplementation and ART, compared with monotherapy, successfully improve cardiac function and alleviate myocardial fibrosis via downregulating TGF-β1, Smad2/3 signaling, and also regulating collagen I and III expressions.