BMP7 Ameliorated Viral Myocardial Fibrosis by Inhibiting Endothelial-to-Mesenchymal Transition

Abstract Background: Endothelial-to-mesenchymal transition (Endo-MT) is associated with myocardial fibrosis in dilated cardiomyopathy (DCM). Endothelial-to-mesenchymal transition (Endo-MT) is induced by coxsackievirus B3 (CVB3) in cardiac microvascular endothelial cells (CMVECs). Bone morphogenetic protein 7 (BMP7) significantly inhibits Endo-MT and the progression of cardiac fibrosis. The study was aimed to investigate the effect and the underlying mechanism of BMP7 on Endo-MT in myocardial fibrosis induce by CVB3 infection in vivo. Methods: BALB/c mice were intraperitoneally injected by CVB3 to induce viral myocarditis (VMC). Mice were treated with BMP7 after CVB3 infection. Subsequently, all groups of mice were determined by echocardiography, histopathologic and molecular detection. Results: We found that the ratio of BMP7/TGF-β1 in mRNA levels was decreased obviously at different time points after CVB3 injection. BMP7 facilitated the recovery of cardiac function after CVB3 infection via inhibition of myocardial damage, collagen deposition. Double immunofluorescence staining indicated that Endo-MT was implicated in CVB3-induced myocardial fibrosis, which was attenuated by BMP7. The protein levels of pSmad3 and Smad4 were significantly upregulated in VMC group, as well as Wnt/β-catenin and the transcription factor snail. BMP7 treatment reversed the changes of these protein levels. Moreover, CO-IP demonstrated the crosstalk between β-catenin and Smad3 in VMC mice, which was downregulated by BMP7 treatment. Conclusions: These results indicated that BMP7 obviously ameliorated myocardial fibrosis in CVB3-infected mice via Endo-MT, which was involved in the TGF-β/Smad and Wnt/β-catenin pathway. β-Catenin/Smad3 interaction may be associated with Endo-MT in the development of viral myocardial fibrosis.