Chronic myocardial ischemia and post-infarction myocardium - expression profiles of genes associated with myocardial fibrosis assessed by oligonucleotide microarray analysis

Abstract

Introduction: Heart failure associated with ischemic heart disease (IHD) is becoming a significant clinical issue. Myocardial remodeling of ischemic etiology tends to result from advanced coronary artery disease (CAD), and especially myocardial infarction which is an extremely potent stimulus of fibrosis. Oligonucleotide microarray analysis allows simultaneous evaluation of the activities of thousands of genes. The method enables one to determine expression profiles of genes typically involved in a given pathology, and allows one to develop an individual treatment strategy depending on the result obtained. The purpose of the study was to use oligonucleotide microarrays to determine expression profiles of genes associated with myocardial fibrosis in a patient with advanced CAD and a history of myocardial infarction, another presenting advanced CAD with no history of myocardial infarction, as well as a subject with normal coronary vessels.
Material and metods: Tissue samples were obtained during elective surgery from the right cardiac auricles of three patients. The expression of 475 genes involved in fibrosis was assessed using the Affymetrix HG-U133A microarray. The patients’ transcriptomes were compared using hierarchical clusterization.
Results and conclusions: Differentiating genes were determined using regression analysis and a Bland- Altman graph analysis. Hierarchical clusterization demonstrated that the profile of gene expression in postinfarction myocardium was different from those in the remaining specimens. Further analysis showed that ENG, GSN, CTGF, and NPPB genes were the differentiating transcripts overexpressed in post-MI, whereas serum/glucocorticoid regulated kinase (SGK) was underexpressed.