Effect of expression of TIMP-1 mRNA on collagen remodeling and relationship between TIMP-1 mRNA and TGF-β_1 in murine hearts with myocarditis

Objective To explore the effect of expression of TIMP-1 mRNA on myocardial collagen remodeling and the relationship between TIMP-1 mRNA and TGF-β1 in a murine model of myocarditis induced by CVB3m. Methods 4-week-old male BALB/c mice were inoculated intraperitoneally with 0.1ml 100 TCID50CVB3m. Age-matched uninfected male mice were used as controls. Animals were killed on the 3, 7, 9,14 ,21, 28 and 56 days after inoculation. Myocardial collagen was stained with VG, and the mRNA expressions of MMP-1, TIMP-1 and TGF-β1 were detected by in situ hybridization. The expression of TGF-β1 was observed by immunohistochemical analysis. Results A significant increase of perivascular collagen area was found in mice myocardium on the 28 days after infection, and on the 56 days both perivascular collagen area and collagen volume fraction in myocardium were obviously increased. The expression of TIMP-1 mRNA was detectable on the 7 days and became significant on days 14 to 21, thereafter attenuated till days 56 after infection. The expression of TGF-β1 mRNA and TGF-β1, which were detectable on the 3 days and had persisted all the experimental course ever since, were most significant on days 14 ~ 21, attenuated thereafter. There was a positive correlation between the expression of TIMP-1 mRNA and TGF-β1(P 0.001). Conclusions The increasing expression of TGF-β1 and up-regulation of TIMP-1 mRNA expression by TGF-β1 may contribute to collagen remodeling in murine hearts with myocarditis induced by CVB3m.