Bone Marrow Mesenchymal Stem Cell Modified with A Disintegrin and Metalloproteinase with Thrombospondin Motifs 1 Inhibitor Regulates Myocardial Fibrosis in Myocarditis

Abstract

This study assesses the mechanism of BMSC modified with ADAMTS-1 inhibitor in regulating the myocardial fibrosis in myocarditis through TGFβ1/MMP9/TIMP1 pathway and collagen metabolism. Model of viral myocarditis (VMC) rats was established and then assigned into control set, carrier set, inhibitor set and carrier and inhibitor set randomly followed by analysis of CVF% in atrial tissue, ADAMTS-1 level by RT-PCR and TGFβ1, MMP9 and TIMP1 level by IHC. ADAMTS-1 mRNA level in control set was highest and lowest in inhibitor set. There was fibrosis in every set inordinately. The degree of myocardial fibrosis was reduced in inhibitor set and carrier and inhibitor set. The quantity of inflammatory cells was also reduced significantly. There was no or sporadic mall focal necrosis. The level of TGFβ1, MMP9 and TIMP1 in the treated three sets was significant decreased compared with control set with more significant changes in the inhibitor set and carrier and inhibitor set. Collagen metabolism in VMC rats was restrained by BMSC modified with ADAMTS-1 inhibitor and therefore the myocardial fibrosis was ameliorated with the possible mechanism being through regulation of the TGFβ1/MMP9/TIMP1 signaling pathway.