Elevation of matrix metalloproteinase-2 level in pericardial fluid is closely associated with left ventricular remodeling

Abstract

The left ventricular (LV) extracellular matrix participates in progressive LV remodeling that is strongly associated with morbidity and mortality in patients with heart failure. Matrix metalloproteinases (MMPs), an endogenous family of zinc-dependent enzymes, increase proteolytic activity in the extracellar spaces, leading to increased extracellular remodeling. 1 Woessner J.F Matrix metalloproteinases and their inhibitors in connective tissue remodeling. FASEB J. 1991; 5: 2145-2154 Crossref PubMed Scopus (3071) Google Scholar , 2 Dollery C.M McEwan J.R Henney A.M Matrix metalloproteinases and cardiovascular disease. Circ Res. 1995; 77: 863-868 Crossref PubMed Scopus (812) Google Scholar Several lines of evidence in experiment animals suggest that MMPs and tissue inhibitors of metalloproteinases (TIMPs) may play an important role in modulating LV remodeling. 3 Thomas C.V Coker M.L Zellner J.L Handy J.R Crumbley A.J Spinale F.G Increased matrix metalloproteinase activity and selective upregulation in LV myocardium from patients with end-stage dilated cardiomyopathy. Circulation. 1998; 97: 1708-1715 Crossref PubMed Scopus (416) Google Scholar , 4 Spinale F.G Coker M.L Krombach S.R Mukherjee R Hallak H Houck W.V Clair M.J Kribbs S.B Johnson L.L Peterson J.T Zile M.R Matrix metalloproteinase inhibition during the development of congestive heart failure effects on left ventricular dimensions and function. Circ Res. 1999; 85: 364-376 Crossref PubMed Scopus (296) Google Scholar In humans, however, little information is available regarding MMPs and TIMPs of cardiac origin in the presence or absence of LV remodeling in patients with ischemic heart disease. It is generally considered that pericardial fluid is not only an ultrafiltrate of plasma, but also a transudate from the cardiac interstitium. 5 Fujita M Komeda M Hasegawa K Kihara Y Nohara R Sasayama S Pericardial fluid as a new material for clinical heart research. Int J Cardiol. 2001; 77: 113-118 Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar Thus, the purposes of this study were: (1) to measure plasma and pericardial fluid levels of total MMP-1 and -2, active MMP-2, and TIMP-1 and -2 in patients with ischemic heart disease, and (2) to investigate their relations to LV volume and function to obtain clinical evidence that MMPs act as autocrine and/or paracrine factors in the process of LV remodeling.