Changes in IGFs in cardiac tissue following myocardial infarction

We have studied changes in the IGF axis in an ovine model of myocardial inf arction (MI), in order to determine the relationship between time-based cha nges in post-infarct myocardium and IGF levels. IGF localization was studie d by immunocytochemistry, production by in situ hybridization, and specific binding by radioligand studies. In surviving tissue, IGF-I peptide localized to cardiomyocytes, with strong est immunostaining at 1 and 2 days post-infarct in the immediate border are a adjoining the infarct, where IGF-I mRNA also increased, reaching a maximu m at 2 days. Binding of radiolabelled IGF-I in surviving tissue was initial ly lower than that seen in cardiomyocytes in control myocardium, subsequent ly increasing to become significantly greater by 6 days post-infarct. In necrotic tissue, IGF-I peptide was still detectable in cardiomyocytes at 0.5 days post-infarct, but had cleared From this area by 1 day, becoming d etectable again at 6 days post-infarct in macrophages and fibroblasts infil trating the repair zone. IGF-I mRNA was not detected in necrotic tissue unt il 6 days, when probe hybridized to macrophages and fibroblasts. Within the necrotic zone, high levels of radiolabelled IGF-I binding to a combination of receptors and binding proteins were observed in cardiomyocytes in islan ds of viable tissue located close to the border. Weak immunostaining for IGF-II was observed in cardiomyocytes of the surviv ing tissue. IGF-II mRNA was not detected in either surviving or necrotic ar eas. Binding of radiolabelled IGF-II was predominantly to macrophages in bo th surviving and infarct areas, although as with IGF-I, high levels of bind ing of radiolabelled IGF-II to a combination of receptors and binding prote ins were observed in islands of viable tissue close to the border within th e necrotic area. We conclude that, following MI, surviving cardiomyocytes at the infarct bor der show marked changes in IGF-I localization, production, and specific bin ding, indicating that the IGF axis is directly involved in post-infarct eve nts, possibly in the maintenance of cardiac function by the induction of hy pertrophy and in cell survival by decreasing apoptotic cell death, which ha s been demonstrated in other cell types.