Expression of theα1andα2Chains of Type IV Collagen in the Infarct Zone of Rat Myocardial Infarction

Healing processes affect ventricular remodeling, an important prognostic factor in acute myocardial infarction (AMI). Type IV collagen, a major component of the basement membrane, has been demonstrated to appear in the infarct zone. Six type IVαchains,α1toα6[α1(IV) toα6(IV)], have been identified. We examined the expression of theα1(IV),α2(IV),α3(IV) andα5(IV) in experimental rat AMI induced by permanent ligation of the left coronary artery in male Sprague–Dawley rats. Neonatal cardiac fibroblasts cultured to reach confluency were also used to examine the hypoxic induction of the expression of these chains. Northern blotting,in situhybridization, and immunohistochemical staining were employed to examine theαchain expression. With thein situhybridization,α1(IV) andα2(IV) mRNA signals were observed in spindle-shaped mesenchymal cells in the intercellular spaces, in the vascular endothelial cells and in some myocytes in the normal myocardium. Signals for bothα1(IV) andα2(IV) mRNA appeared in the spindle-shaped mesenchymal cells located between the surviving myocytes in the infarct peripheral zone at 24 h after the ligation. These signals extended into the central zone and reached the center point of the infarct 5 days after the ligation. Neitherα3(IV) norα5(IV) mRNA signals were observed in the infarct zone. Northern blotting demonstrated increased expressions ofα1(IV) andα2(IV) mRNA in the infarct zone compared to the sham-operated hearts. The expression ofα5(IV) mRNA was weak in the sham-operated hearts but was not detected in the infarct zone.α3(IV) mRNA was not expressed in the infarct zones or sham-operated hearts. In the cultured cardiac fibroblasts, a hypoxic induction of the expression of bothα1(IV) andα2(IV) mRNA was demonstrated by Northern hybridization. Immunohistochemistry revealedα1(IV) andα2(IV) staining in the infarct lesion. The findings demonstrate that among the type IV collagenαchains examined,α1(IV) andα2(IV) produced by mesenchymal cells appeared in the infarct zone, suggesting that type IV collagen composed byα1andα2chains contributes to the pathological course of myocardial infarction.