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Published on: August 17, 2022
Identification and validation of potential hypoxia-related genes associated with coronary artery disease
Yuqing Jin1, Weiyan Ren1, Jiayi Liu1
1Department of Epidemiology, School of Public Health, Hebei Medical University, Shijiazhuang, China.
Insights
This study identifies four key hypoxia genes linked to coronary artery disease (CAD). These findings offer new insights into hypoxia
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Genomics
Background:
- Coronary artery disease (CAD) is a major cause of death, with hypoxia playing a significant role in its development and patient outcomes.
- The precise involvement of hypoxia in CAD pathogenesis remains incompletely understood.
Purpose of the Study:
- To identify and validate hypoxia-related genes associated with CAD.
- To explore the functional roles and potential therapeutic targets of these genes in CAD.
Main Methods:
- Utilized microarray datasets (GSE113079) and hypoxia gene sets for differential analysis.
- Applied machine learning to screen for hub genes and validated findings across multiple datasets.
- Conducted Gene Ontology (GO) and KEGG pathway enrichment analyses, alongside immune cell infiltration and single-cell sequencing analyses.
Main Results:
- Identified 54 differentially expressed hypoxia-related genes (DE-HRGs) and four hub genes: ADM, PPFIA4, FAM162A, and TPBG.
- Found three upregulated hub genes (ADM, PPFIA4, TPBG) correlated with metabolic genes; all four enriched in immune-related pathways.
- Observed significant differences in immune cell types, particularly CD8 T cells, and higher expression of ADM, FAM162A, and TPBG in endothelial cells of CAD patients.
Conclusions:
- Four hypoxia genes (ADM, PPFIA4, FAM162A, TPBG) are identified as potential biomarkers and therapeutic targets for CAD.
- The study highlights the intricate relationship between hypoxia, immune responses, and metabolic alterations in CAD.
- Findings contribute to understanding the hypoxia landscape in CAD and suggest avenues for future research and treatment development.
Abstract:
Introduction: Coronary artery disease (CAD) is one of the most life-threatening cardiovascular emergencies with high mortality and morbidity. Increasing evidence has demonstrated that the degree of hypoxia is closely associated with the development and survival outcomes of CAD patients. However, the role of hypoxia in CAD has not been elucidated. Methods: Based on the GSE113079 microarray dataset and the hypoxia-associated gene collection, differential analysis, machine learning, and validation of the screened hub genes were carried out. Results: In this study, 54 differentially expressed hypoxia-related genes (DE-HRGs), and then 4 hub signature genes (ADM, PPFIA4, FAM162A, and TPBG) were identified based on microarray datasets GSE113079 which including of 93 CAD patients and 48 healthy controls and hypoxia-related gene set. Then, 4 hub genes were also validated in other three CAD related microarray datasets. Through GO and KEGG pathway enrichment analyses, we found three upregulated hub genes (ADM, PPFIA4, TPBG) were strongly correlated with differentially expressed metabolic genes and all the 4 hub genes were mainly enriched in many immune-related biological processes and pathways in CAD. Additionally, 10 immune cell types were found significantly different between the CAD and control groups, especially CD8 T cells, which were apparently essential in cardiovascular disease by immune cell infiltration analysis. Furthermore, we compared the expression of 4 hub genes in 15 cell subtypes in CAD coronary lesions and found that ADM, FAM162A and TPBG were all expressed at higher levels in endothelial cells by single-cell sequencing analysis. Discussion: The study identified four hypoxia genes associated with coronary heart disease. The findings provide more insights into the hypoxia landscape and, potentially, the therapeutic targets of CAD.
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