COLLAGEN REMODELING AFTER MYOCARDIAL-INFARCTION IN THE RAT-HEART

In this study changes in the amount and distribution of types I and II I collagen mRNA and protein were investigated in the rat heart after i nduction of a left ventricular myocardial infarction (MI). Sham operat ed mts served as controls. The animals were sacrificed at different ti me intervals after operation Northern blotting of cardiac RNA and hybr idization with cDNA probes for types I and III procollagen revealed a 5- to 15-fold increase in the infarcted left ventricle. Type III proco llagen mRNA levels were already increased at day 2 after MI, whereas t ype I procollagen mRNA followed this response at day 4 after MI, This increase was sustained for at least 21 days in the infarcted left vent ricle for type III procollagen mRNA, whereas type I procollagen mRNA l evels were still elevated at 90 days after MI lit the noninfarcted rig ht 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 n on-infarcted septum a transient increase was observed for type I proco llagen mRNA from day 7-21 (4- to 5-fold increase) and a decline to sha m levels thereafter, In the septum type III procollagen mRNA levels we re only elevated at 7 days after MI (4- to 5-fold increase) compared w ith sham operated controls. Ln situ hybridization with the same types I and III procollagen probes showed procollagen mRNA-producing cells i n the infarcted area around necrotic cardiomyocytes, and in the inters titial cells in the non-infarcted part of the myocardium No labeling w as detected above cardiomyocytes. Combined in situ hybridization and i mmunohistochemistry showed that the collagen mRNA producing cells have a myofibroblast-like phenotype in the infarcted myocardium and are fi broblasts in the non-infarcted septum and right ventricle. The increas e in types I and III procollagen mRNA in both infarcted and non-infarc ted myocardium was followed by an increased collagen deposition, measu red by computerized morphometry on sirius red-stained tissue sections as well as by the hydroxyproline assay, In the non-infarcted septum an d 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 A 2.3-fold increas e was found 14 days after MI, while in the infarcted areas 3- and 8.2- fold increases were found 7 and 14 days after MI, respectively. We con clude that types I and III procollagen mRNA and protein content increa se in both the infarcted and non-infarcted parts of the myocardium aft er MI, Interstitial cells and not cardiomyocytes produce these collage ns, myofibroblasts in the infarcted and fibroblasts in the non-infarct ed myocardium.