Based on these findings, myocarditis-disrupted TIMP-3-MMP-2 regulatory pathway as well as increased expression of MMP-2 may lead to the degradation of myocardial ECM that in turn promotes ventricular remodeling and stimulates new synthesis type I and III collagen25,32, resulting in the development of DCM, while stimulating EP4 receptor to suppress MMP-2 expression and positively regulate TIMP-3 expression may prevent DCM after myocarditis by depriving MMP-2 of its ability to degrade myocardial ECM (Supplementary Fig. 5). This evidence concerns the gene MMP2 and familial dilated cardiomyopathy.