Myocardial gene expression of hibernating and control tissue from patients with ischemic left ventricular dysfunction. Homo sapiens

Objectives: While cardiac scar tissue is damaged irreversibly, hibernating myocardium is characterized by reversible contractile dysfunction. Limited data are available in humans regarding the molecular biology of hibernating myocardium. The aim of this study was to identify new molecular mechanisms distinctive for human hibernating myocardium by gene expression analysis. Results: Of 4,171 transcripts examined, we identified 86 to be differentially expressed. Twentyone genes showed an increased and 65 genes a decreased expression in hibernating myocardium. Functional clustering revealed major changes in the expression of genes associated with transcription, protein modification and phosphorylation, regulation of apoptosis and intercellular communication. Besides the reported upregulation of ß-adrenergic receptor kinase-1 in heart failure, we observed new gene expression patterns, such as the upregulation of fas-activated serine/threonine kinase (FAST) or reduced expression of desmoplakin. Downregulation of desmoplakin in cardiomyocytes from hibernating myocardium was also seen on the protein level, consistent with a role of this protein in the development of a dilative cardiomyopathy. Conclusions: Gene expression analysis of hibernating myocardium provided novel insights into the molecular mechanisms underlying ischemic heart failure. Dysfunction of desmosomes may contribute to impaired contractility and dilative tissue remodeling. Keywords: disease state analysis Overall design: Methods: We compared in patients with advanced coronary artery disease and impaired left ventricular function the gene expression profile of myocardial biopsies from hibernating myocardium (n=5), as identified in PET by a mismatch between perfusion and glucose metabolism, with expression profiles of matched biopsies from remote myocardium. Gene-specific PCR of selected genes was used to validate our technical approach. Immunohistochemical staining was performed for one gene of specific interest.