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Published on: January 28, 2020
Gene expression profiling of CD133-positive cells in coronary artery disease
Jiayu Li1, Changyu Zhou2, Jiarui Li3
1Department of Cardiology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.
Insights
Exercise partially normalizes gene expression in coronary artery disease (CAD) patients by altering key genes. These findings suggest potential therapeutic targets and small molecules for cardiac therapy.
Area of Science:
- Cardiovascular Biology
- Molecular Genetics
- Exercise Physiology
Background:
- Coronary artery disease (CAD) involves complex genetic alterations.
- CD133-positive cells are implicated in cardiac repair and disease.
- Understanding gene expression changes in CAD is crucial for developing effective therapies.
Purpose of the Study:
- To identify key genes in CD133-positive cells associated with CAD.
- To investigate the impact of exercise on gene expression profiles in CAD patients.
- To explore potential therapeutic small molecules targeting CAD-related genes.
Main Methods:
- Analysis of gene expression profiles from healthy controls and CAD patients (baseline and post-exercise).
- Utilized R packages (limma, pheatmap) for differential gene expression and cluster analysis.
- Functional enrichment analysis (DAVID) and small molecule prediction (cMap) were performed.
Main Results:
- Identified 131 differentially expressed genes (DEGs) at baseline and 71 after exercise in CAD patients.
- 44 overlapping DEGs were found, effectively distinguishing CAD patients from controls via cluster analysis.
- Enriched pathways included response to peptide hormone stimulus and anti-apoptosis; 12 potential small molecules (e.g., MG-262) were identified.
Conclusions:
- Three months of exercise partially normalized gene expression in CAD patients.
- Common DEGs highlight pathways crucial for cardiac health and disease.
- Specific genes unaffected by exercise may represent targets for novel small molecule therapies in CAD.
Abstract:
Gene expression profiles of CD133-positive cells from patients with coronary artery disease (CAD) were analyzed to identify key genes associated with cardiac therapy. Furthermore, the effect of exercise on gene expression was also investigated. Gene expression data set (accession number: GSE18608) was downloaded from the Gene Expression Omnibus, including blood samples from four healthy subjects (H), and from 10 patients with coronary artery disease at baseline (B) and after 3 months (3M) of exercise. Differential analysis was performed for H vs. B and H vs. 3M using limma package of R. Two‑way cluster analysis was performed using the expression levels of the differentially expressed genes (DEGs) by package pheatmap of R. Functional enrichment analysis was applied on the DEGs using the Database for Annotation, Visualization and Integrated Discovery. Relevant small molecules were predicted using the Connectivity map database (cMap). A total of 131 and 71 DEGs were identified in patients with CAD prior to and following 3 months of exercise. The two groups of DEGs were compared and 44 genes overlapped. In cluster analysis with the expression levels of the common DEGs, patients with CAD could be well separated from the healthy controls. Functional enrichment analysis showed that response to peptide hormone stimulus and anti‑apoptosis pathways were significantly enriched in the common DEGs. A total of 12 relevant small molecules were revealed by cMap based upon the expression levels of common DEGs, such as 5252917 and MG‑262. Three months of exercise in part normalized the gene expression in CAD patients. The genes not altered by exercise may be the targets of small molecules, such as 5252917 and MG-262.
