A matrix metalloproteinase induction/activation system exists in the humanleft ventricular myocardium and is upregulated in heart failure

Background-Matrix metalloproteinases (MMPs) contribute to matrix remodeling in disease states such as tumor metastases. Extracellular matrix metallopr oteinase inducer (EMMPRIN) has been reported to increase MMP expression, an d membrane-type MMP or MT1-MMP has been implicated to activate MMPs. The pr esent study examined whether and to what degree EMMPRIN and MT1-MMP were ex pressed in human left ventricular (LV) myocardium as well as the associatio n with MMP activity and expression in dilated cardiomyopathy (DCM). Methods and Results-LV myocardial zymographic MMP activity increased by >2- fold with both nonischemic DCM (n=21) and ischemic DCM (n=16) compared with normal (n=13). LV myocardial abundance of MMP-9 was increased with both fo rms of DCM. MMP-2 and MMP-3 were increased with nonischemic DCM, MMP-1 leve ls were decreased with both forms of DCM. EMMPRIN increased by >250% and MT 1-MMP increased by >1000% with both farms of DCM. Conclusions-Increased LV myocardial MMP activity and selective upregulation of MMPs with nonischemic and ischemic forms of DCM occurred. Moreover, a l ocal MMP induction/activation system was identified in isolated normal huma n LV myocytes that was upregulated with DCM. The control of MMP activation and expression in the failing human LV myocardium represents a new and pote ntially significant therapeutic target for this disease process.