Changes in extracellular matrix and in transforming growth factor beta isoforms after coronary artery ligation in rats.
Extensive myocardial remodeling occurs after transmural myocardial infarction (MI). The infarcted myocardium is being replaced by scar tissue after gradual resorption of the necrotic tissue. The remodeling process involves both synthesis and degradation of collagens as major components of the extracellular matrix (ECM). In the present study we have analyzed the time-dependent changes of the processes related to this fibrosis in the infarct area and in the non-infarcted left ventricle (LV) six hours to 82 days after occlusion of the left anterior descending coronary artery (LAD) in rats. We also examined whether changes occurred in the expression pattern of the transforming growth factor (TGF) beta isoforms, since this cytokine is known as powerful inductor of fibrosis. Elevation in colligin expression preceded the pronounced increase in mRNA expression of both type I and type III collagen after MI from day three onwards. The maximal increase in colligin protein in the infarct area coincided with the most pronounced expression of collagen I and collagen III mRNA expression. Also, the expression and activity of matrix metalloproteinases (MMPs) and of tissue inhibitor of matrix metalloproteinase (TIMP)-2 mRNA were increased predominantly in the infarct area. TGF beta(1)and TGF-beta(2)expression increased within the first days after MI, whereas TGF-beta(3)expression was elevated predominantly in the infarct area. This pronounced increase in TGF-beta(3)persisted up to 82 days and correlated positively with the parameters of ECM metabolism. Thus, the scar formation is an ongoing dynamic process in which TGF-beta(3)seems to play an active role in the complex ventricular remodeling.
Deten
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Carl-Ludwig-Institute of Physiology, University of Leipzig, Germany. deta@medizin.uni-leipzig.de
Hölzl
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Leicht
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Barth
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Zimmer
H G
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D000818:Animals; D001158:Arteries; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D003094:Collagen / Q000235:genetics; D003331:Coronary Vessels; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D005780:Gelatin / Q000378:metabolism; D015870:Gene Expression; D006023:Glycoproteins; D006439:Hemodynamics; D017380:Hypertrophy, Right Ventricular / Q000378:metabolism / Q000503:physiopathology; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020784:Matrix Metalloproteinase 8 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D009203:Myocardial Infarction / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger; D051381:Rats; D017207:Rats, Sprague-Dawley; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D053782:Transforming Growth Factor beta3; D018487:Ventricular Dysfunction, Left / Q000378:metabolism / Q000503:physiopathology; D018497:Ventricular Dysfunction, Right / Q000378:metabolism / Q000503:physiopathology
D002352:Carrier Proteins; D006023:Glycoproteins; D020033:Protein Isoforms; D012333:RNA, Messenger; C508962:Tgfb1 protein, rat; C509046:Tgfb3 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D053782:Transforming Growth Factor beta3; C046289:colligin; D019716:Tissue Inhibitor of Metalloproteinase-2; D005780:Gelatin; D003094:Collagen; D020778:Matrix Metalloproteinase 2; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9