In conclusion, the present study using EAM mice delineated for the first time that myocardial ECM metabolism by persistent activation of MMP-2 is an important and novel molecular mechanism underlying adverse ventricular remodeling after myocarditis and that continued treatment with selective EP4 receptor stimulant rescues cardiac malfunction during myocarditis and exhibits robust preventive effects against adverse ventricular remodeling and cardiac fibrosis after myocarditis in association with the TIMP-3-MMP-2 regulatory pathway. This evidence concerns the gene TIMP3 and myocarditis.