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Murine Myocardial Infarction Model using Permanent Ligation of Left Anterior Descending Coronary Artery
Published on: August 16, 2019
Oligonucleotide microarray analysis of genes regulating apoptosis in chronically ischemic and postinfarction
Józefa Dabek1, Aleksander Owczarek, Zbigniew Gasior
1Department of Cardiology, Medical University of Silesia, Ziołowa 47, Katowice, Poland.
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.
Insights
This study investigated apoptosis-regulating gene expression in post-myocardial infarction (MI) heart tissue. Key findings reveal distinct gene profiles, with CFLAR overexpression potentially driving apoptosis in post-MI cardiac tissue.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Gene Expression Profiling
Background:
- Cardiomyocyte death post-myocardial infarction (MI) involves necrosis and apoptosis.
- Apoptosis presents a therapeutic target for influencing cell death pathways.
- Understanding apoptosis-regulating gene expression is crucial for developing novel treatments.
Purpose of the Study:
- To determine the expression profiles of apoptosis-regulating genes in post-MI myocardium.
- To compare gene expression between chronically ischemic and healthy heart muscle.
- To identify specific genes involved in apoptosis post-MI.
Main Methods:
- Oligonucleotide microarrays (Affymetrix HG_U133A) were used to assess 141 fibrosis-related genes.
- Transcriptomes from post-MI and healthy myocardium were compared.
- Hierarchical clusterization, regression analysis, and Bland-Altman analysis were employed.
Main Results:
- Gene expression profiles differed significantly between post-MI and healthy myocardium.
- FOXO3A was underexpressed, while CFLAR was overexpressed in post-MI samples.
- Significant differences in apoptosis-regulating gene expression were observed.
Conclusions:
- Apoptosis-regulating gene expression is significantly altered in post-MI myocardium.
- The gene CFLAR plays a crucial role in inducing apoptosis in post-MI cardiac tissue.
- These findings may inform future therapeutic strategies targeting post-infarction cardiac remodeling.
