Oligonucleotide microarray analysis of genes regulating apoptosis in chronically ischemic and postinfarction myocardium

Abstract

The pathology of cardiomyocyte death during and after myocardial infarction involves both necrosis and apoptosis. Although both mechanisms lead to cell death, participation of apoptosis in this process carries the potential of developing therapies influencing at least part of the population of dying cells. Therefore the aim of this study was to determine (using oligonucleotide microarrays) expression profiles of apoptosis-regulating genes in postinfarction myocardium, comparing chronically ischemic and healthy heart muscle. Tissue samples were obtained during elective surgery from the right cardiac auricles of three patients. The expression of 141 genes involved in fibrosis was assessed using the Affymetrix HG_U133A microarray. The patients' transcriptomes were compared using hierarchical clusterization. Differentiating genes were determined using regression analysis and Bland-Altman graph analysis. Hierarchical clusterization demonstrated that the profile of gene expression in postinfarction myocardium was different from that in the remaining specimens. Further statistical analysis showed two important differentiating genes: FOXO3A (underexpressed in post-MI sample) and CFLAR (overexpressed in post-MI sample). The expression of apoptosis-regulating genes is significantly different in post-MI myocardium from chronically ischemic and a nonischemic myocardium. Our results suggest that CFLAR is important in the induction of apoptosis in postinfarction cardiac tissue.