A matrix metalloproteinase induction/activation system exists in the human left 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 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).


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.
Spinale
F G
FG
Medical University of South Carolina, Charleston 29425, USA.
Coker
M L
ML
Heung
L J
LJ
Bond
B R
BR
Gunasinghe
H R
HR
Etoh
T
T
Goldberg
A T
AT
Zellner
J L
JL
Crumbley
A J
AJ
D000293:Adolescent; D000328:Adult; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D051926:Basigin; D002311:Cardiomyopathy, Dilated / Q000201:enzymology* / Q000473:pathology; D004789:Enzyme Activation; D004790:Enzyme Induction; D006352:Heart Ventricles / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D015151:Immunoblotting; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000096:biosynthesis*; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D012508:Sarcolemma / Q000201:enzymology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism / Q000494:pharmacology; D015854:Up-Regulation
D015703:Antigens, CD; D000951:Antigens, Neoplasm; C497886:BSG protein, human; D061965:Matrix Metalloproteinase Inhibitors; D008562:Membrane Glycoproteins; D019715:Tissue Inhibitor of Metalloproteinase-1; D051926:Basigin; D020782:Matrix Metalloproteinases