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.

Long non-coding RNA-ROR aggravates myocardial ischemia/reperfusion injury

“…Myocardial ischemia/reperfusion (I/R) injury leads to adverse cardiovascular outcomes following myocardial ischemia, cardiac surgery or circulatory arrest and is one of the major causes of morbidity and mortality in humans with coronary heart disease ( 1 ). The pathology of the disease suggests that myocardial infarction and angina pectoris are accompanied by changes in gene expression ( 2 ). The underlying molecular mechanisms of myocardial I/R injury are complex and include oxidative stress, intracellular Ca 2+ overload, rapid restoration of physiological pH upon reperfusion, mitochondrial permeability transition pore, and exaggerated inflammation ( 3 ).…”

Genetic association of FOXO1A and FOXO3A with longevity trait in Han Chinese populations

“…Malfunctions of FOXO1A or FOXO3A are involved in various cancers, insulin resistance, altered immune responses and organ damage (15,22,37 -40). In the cardiovascular system, for example, FOXO1A and/or FOXO3A are/is important for the onset of diabetic cardiomyopathy (41,42), cardiac hypertrophy (43,44) and ischemic heart disease (45,46). It is likely that FOXO1A and FOXO3A affect longevity through multiple pathways, such as insulin resistance, stress responses or proneness to disease.…”

Forkhead box transcription factor 1: role in the pathogenesis of diabetic cardiomyopathy

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