Changes in extracellular matrix and in transforming growth factor beta isoforms after coronary artery ligation in rats

Extensive myocardial remodeling occurs after transmural myocardial infarcti on (MI). The infarcted myocardium is being replaced by scar tissue after gr adual resorption of the necrotic tissue. The remodeling process involves bo th synthesis and degradation of collagens as major components of the extrac ellular matrix (ECM). In the present study we have analyzed the time-depend ent changes of the processes related to this fibrosis in the infarct area a nd in the non-infarcted left ventricle (LV) six hours to 82 days after occl usion of the left anterior descending coronary artery (LAD) in rats. We als o examined whether changes occurred in the expression pattern of the transf orming growth factor (TGF) beta isoforms, since this-cytokine is known as p owerful inductor of fibrosis. Elevation in colligin expression preceded the pronounced increase in mRNA expression of both type I and type III collage n after MI from day three onwards. The maximal increase in colligin protein in the infarct area coincided with the most pronounced expression of colla gen I and collagen III mRNA expression. Also, the expression and activity o f matrix metalloproteinases (MMPs) and of tissue inhibitor of matrix metall oproteinase (TIMP)-2 mRNA were increased predominantly in the infarct area. TGF beta (1) and TGF-beta (2) expression increased within the first days a fter MI, whereas TGF-beta (3) expression was elevated predominantly in the infarct area. This pronounced increase in TGF-beta (3) Persisted up to 82 d ays and correlated positively with the parameters of ECM metabolism. Thus, the scar formation is an ongoing dynamic process in which TGF-beta (3) seem s to play an active role in the complex ventricular remodeling. (C) 2001 Ac ademic Press.