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

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Abstract

Background - Matrix metalloproteinases (MMPs) contribute to matrix remodeling in disease states such as tumor metastases. Extracellular matrix metalloproteinase inducer (EMMPRIN) has been reported to increase MMP expression, and membrane-type MMP or MT1-MMP has been implicated to activate MMPs. The present study examined whether and to what degree EMMPRIN and MT1-MMP were expressed in human left ventricular (LV) myocardium as well as the association 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 forms of DCM. MMP-2 and MMP-3 were increased with nonischemic DCM. MMP-1 levels were decreased with both forms of DCM. EMMPRIN increased by >250% and MT1-MMP increased by >1000% with both forms of DCM. Conclusions - Increased LV myocardial MMP activity and selective upregulation of MMPs with nonischemic and ischemic forms of DCM occurred. Moreover, a local MMP induction/activation system was identified in isolated normal human LV myocytes that was upregulated with DCM. The control of MMP activation and expression in the failing human LV myocardium represents a new and potentially significant therapeutic target for this disease process.

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Spinale, F. G., Coker, M. L., Heung, L. J., Bond, B. R., Gunasinghe, H. R., Etoh, T., … Crumbley, A. J. (2000). A matrix metalloproteinase induction/activation system exists in the human left ventricular myocardium and is upregulated in heart failure. Circulation, 102(16), 1944–1949. https://doi.org/10.1161/01.CIR.102.16.1944

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