Objective: To investigate the relationship between endothelial-to-mesenchymal transition (EndMT) and myocardial fibrosis in acute viral myocarditis (VMC).
Methods: Twenty-eight Balb/c mice were randomized into 3 groups: control group (n=8), VMC group(n=10) and intervention group(n=10). Mice in VMC and intervention groups were injected intraperitoneally(i.p) with single dose of coxsackievirus B3, mice in control group were injected with equal amount of viral-free vehicle. In the following day, mice in control and VMC groups were injected i.p with 0.1 ml of saline and intervention group with 0.1 ml of recombinant human bone morphogenetic protein 7(rh-BMP7) at a concentration of 300 μg/kg. The mice hearts were harvested after 7 d, cardiac collagen volume fraction (CVF) was calculated on picrosirius red-stained sections. mRNA and protein expression of TGF-β1, CD31, VE-cadherin, fibroblast special protein 1 (FSP-1) and α-smooth muscle actin (α-SMA) and collagen 1α1 in myocardiac tissues were detected by real-time RT-PCR and Western blot analysis, respectively.
Results: Compared to controls, overt fibrosis was presented in necrotic area of myocardium in VMC group. Meanwhile, marked increase of TGF-β1 expression accompanied with EndMT characterized by loss of endothelial phenotype (decreased expression of CD31 and VE-cadherin), gain of mesenchymal proteins (overexpression of FSP-1 and α-SMA) and increased synthesis of collagen was also demonstrated. Both EndMT and cardiac fibrosis were simultaneously reversed by TGF-β1 inhibition.
Conclusion: EndMT is involved in cardiac fibrosis in acute viral myocarditis, TGF-β1 might be a main mediator.