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Identification of Hypoxia-related Genes in Acute Myocardial Infarction using Bioinformatics Analysis
Huasong Xia1, Yi Chen1, Qiang Chen2
1Department of Cardiology, Second Affiliated Hospital of Nanchang University, 330006, No. 1 Mingde Road, Nanchang, Jiangxi, China.
Background:
Acute myocardial infarction (AMI) remains one of the most fatal diseases worldwide. Persistent ischemia and hypoxia are implicated as significant mechanisms in the development of AMI. However, no hypoxia-related gene targets of AMI have been identified to date. This study aimed to identify potential genes and drugs for AMI using bioinformatics analysis.
Materials And Methods:
Two datasets both related to AMI (GSE76387 and GSE161427) were downloaded from the Gene Expression Omnibus to identify differentially expressed genes (DEGs) between AMI and sham mice. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. A protein-protein interaction (PPI) network was constructed to identify hub genes using Cytoscape. Candidate genes were identified by the intersection of hub genes and hypoxia-related genes. Western blotting was used to validate the candidate genes in the AMI mouse model. Furthermore, the Drug-Gene Interaction Database was used to predict potential therapeutic drugs targeting all hub genes.
Results:
Fifty-three upregulated and 16 downregulated genes closely related to AMI were identified. The DEGs were primarily enriched in protein, heparin, and integrin binding. KEGG analysis suggested that focal adhesion, PI3K-Akt signaling pathway, and extracellular matrix-receptor interaction are crucial pathways for AMI. The PPI network analysis identified 14 hub genes, two of which were hypoxia-related. Several agents were found to have therapeutic potential for AMI.
Conclusion:
This study suggests that connective tissue growth factors and the collagen family members may be candidate targets in treating AMI. Agents targeting these candidates may be potential treatments.
Insights
Researchers identified novel hypoxia-related genes, including connective tissue growth factors and collagen, as potential therapeutic targets for acute myocardial infarction (AMI). This study offers new avenues for treating this fatal cardiovascular disease.
Area of Science:
- Cardiovascular Research
- Genomics
- Bioinformatics
Background:
- Acute myocardial infarction (AMI) is a leading cause of global mortality.
- Persistent ischemia and hypoxia are key mechanisms in AMI development.
- No specific hypoxia-related gene targets for AMI have been identified previously.
Purpose of the Study:
- To identify potential gene targets and therapeutic drugs for AMI using bioinformatics.
- To uncover hypoxia-related genes implicated in AMI pathogenesis.
Main Methods:
- Differential gene expression analysis of AMI and sham mouse datasets (GSE76387, GSE161427).
- Gene Ontology and KEGG pathway enrichment analyses.
- Protein-protein interaction network construction to identify hub genes.
- Validation of candidate genes and prediction of therapeutic drugs.
Main Results:
- Identified 53 upregulated and 16 downregulated genes associated with AMI.
- Key enriched pathways include focal adhesion and PI3K-Akt signaling.
- Discovered 14 hub genes, with two identified as hypoxia-related.
- Several potential therapeutic agents targeting hub genes were predicted.
Conclusions:
- Connective tissue growth factors and collagen family members are proposed as candidate targets for AMI treatment.
- Targeting these identified genes may offer potential therapeutic strategies for AMI.
