Title:Identification of Hypoxia-related Genes in Acute Myocardial Infarction
using Bioinformatics Analysis
Volume: 26
Issue: 4
Author(s): Huasong Xia, Yi Chen, Qiang Chen and Yanqing Wu*
Affiliation:
- Department of Cardiology, Second Affiliated Hospital of Nanchang University, 330006, No. 1 Mingde Road,
Nanchang, Jiangxi, China
Keywords:
Acute myocardial infarction, microarray expression profile, differentially expressed genes, hypoxia-related genes, protein-protein interaction network, AMI.
Abstract:
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.