Identification and validation of hub genes involved in foam cell formation and atherosclerosis development via bioinformatics

Da Teng; Hongping Chen; Wenjuan Jia; Qingmiao Ren; Xiaoning Ding; Lihui Zhang; Lei Gong; Hua Wang; Lin Zhong; Jun Yang

doi:10.7717/peerj.16122

Identification and validation of hub genes involved in foam cell formation and atherosclerosis development via bioinformatics

PeerJ. 2023 Oct 3:11:e16122. doi: 10.7717/peerj.16122. eCollection 2023.

Authors

Da Teng^#^{1

2}, Hongping Chen^#³, Wenjuan Jia^{1

2}, Qingmiao Ren⁴, Xiaoning Ding¹, Lihui Zhang^{1

2}, Lei Gong¹, Hua Wang¹, Lin Zhong¹, Jun Yang^{1

2}

Affiliations

¹ Yantai Yuhuangding Hospital Affiliated to Qingdao University, Yantai, China.
² Qingdao University, Qingdao, China.
³ Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
⁴ The Precision Medicine Laboratory, The First Hospital of Lanzhou University, Lanzhou, China.

^# Contributed equally.

Abstract

Background: Foam cells play crucial roles in all phases of atherosclerosis. However, until now, the specific mechanisms by which these foam cells contribute to atherosclerosis remain unclear. We aimed to identify novel foam cell biomarkers and interventional targets for atherosclerosis, characterizing their potential mechanisms in the progression of atherosclerosis.

Methods: Microarray data of atherosclerosis and foam cells were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expression genes (DEGs) were screened using the "LIMMA" package in R software. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and Gene Ontology (GO) annotation were both carried out. Hub genes were found in Cytoscape after a protein-protein interaction (PPI) enrichment analysis was carried out. Validation of important genes in the GSE41571 dataset, cellular assays, and tissue samples.

Results: A total of 407 DEGs in atherosclerosis and 219 DEGs in foam cells were identified, and the DEGs in atherosclerosis were mainly involved in cell proliferation and differentiation. CSF1R and PLAUR were identified as common hub genes and validated in GSE41571. In addition, we also found that the expression of CSF1R and PLAUR gradually increased with the accumulation of lipids and disease progression in cell and tissue experiments.

Conclusion: CSF1R and PLAUR are key hub genes of foam cells and may play an important role in the biological process of atherosclerosis. These results advance our understanding of the mechanism behind atherosclerosis and potential therapeutic targets for future development.

Keywords: Bioinformatics; Cardiovascular disease (CVD); Foam cells; Lipid metabolism.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Atherosclerosis* / genetics
Computational Biology / methods
Foam Cells
Gene Expression Profiling* / methods
Humans
Protein Interaction Maps / genetics
Receptor Protein-Tyrosine Kinases / genetics
Receptors, Colony-Stimulating Factor / genetics

Substances

Receptor Protein-Tyrosine Kinases
Receptors, Colony-Stimulating Factor

Grants and funding

Funding was provided by the National Natural Science Foundation of China (No. 82200503) and the National Natural Science Foundation of Shandong Province (No. ZR2022MH151 and ZR2022QH237). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.