Collagen remodeling after myocardial infarction in the rat heart.
- 1 August 1995
- journal article
- Vol. 147 (2), 325-38
Abstract
In this study changes in the amount and distribution of types I and III collagen mRNA and protein were investigated in the rat heart after induction of a left ventricular myocardial infarction (MI). Sham operated rats served as controls. The animals were sacrificed at different time intervals after operation. Northern blotting of cardiac RNA and hybridization with cDNA probes for types I and III procollagen revealed a 5- to 15-fold increase in the infarcted left ventricle. Type III procollagen mRNA levels were already increased at day 2 after MI, whereas type I procollagen mRNA followed this response at day 4 after MI. This increase was sustained for at least 21 days in the infarcted left ventricle for type III procollagen mRNA, whereas type 1 procollagen mRNA levels were still elevated at 90 days after MI. In the noninfarcted right ventricle a 5- to 7-fold increase was observed for both type I and type III procollagen mRNA levels, but only at day 4 after MI. In the non-infarcted septum a transient increase was observed for type I procollagen mRNA from day 7-21 (4- to 5-fold increase) and a decline to sham levels thereafter. In the septum type III procollagen mRNA levels were only elevated at 7 days after MI (4- to 5-fold increase) compared with sham operated controls. In situ hybridization with the same types I and III procollagen probes showed procollagen mRNA-producing cells in the infarcted area around necrotic cardiomyocytes, and in the interstitial cells in the non-infarcted part of the myocardium. No labeling was detected above cardiomyocytes. Combined in situ hybridization and immunohistochemistry showed that the collagen mRNA producing cells have a myofibroblast-like phenotype in the infarcted myocardium and are fibroblasts in the noninfarcted septum and right ventricle. The increase in types I and III procollagen mRNA in both infarcted and non-infarcted myocardium was followed by an increased collagen deposition, measured by computerized morphometry on sirius red-stained tissue sections as well as by the hydroxyproline assay. In the non-infarcted septum and right ventricle the collagen-positive area was maximal at day 14 (3- to 5-fold increase compared with sham operated controls) and slightly declined at day 21. In the infarcted myocardium the collagen-positive area was 57 +/- 10% at day 14 after MI. Hydroxyproline contents were significantly increased in the noninfarcted septum.(ABSTRACT TRUNCATED AT 400 WORDS)This publication has 55 references indexed in Scilit:
- Interstitial Collagen is Increased in the Non-infarcted Human Myocardium After Myocardial InfarctionJournal of Molecular and Cellular Cardiology, 1993
- Transforming growth factor-beta 1 induces alpha-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblastsThe Journal of cell biology, 1993
- Regulation of procollagen metabolism in the pressure-overloaded rat heart.JCI Insight, 1993
- Alteration of collagen phenotypes in ischemic cardiomyopathy.JCI Insight, 1991
- Enhanced deposition of predominantly type I collagen in myocardial diseaseJournal of Molecular and Cellular Cardiology, 1990
- Acute hemodynamic effects of coronary artery ligation in conscious ratsBasic Research in Cardiology, 1990
- Reappearance of an embryonic pattern of fibronectin splicing during wound healing in the adult rat.The Journal of cell biology, 1989
- Studies on collagen in the experimental myocardial infarction.Japanese Circulation Journal, 1985
- Early degradation of collagen after acute myocardial infarction in the ratThe American Journal of Cardiology, 1983
- The role of local disparity in conduction and recovery time on ventricular vulnerability to fibrillationAmerican Heart Journal, 1977