Integrated Assessment of Macrophage Lipids Homeostasis Omics Data: Identification of Potential Genes and Pathways in Atherosclerosis

Abstract

Atherosclerosis is a chronic inflammatory disease characterized by the formation of lipid-rich plaques within the arterial wall. Increasing evidences have shown that cellular senescence may contribute to the progression of atherosclerosis, but the mechanism remains unclear. Hence, the present study aimed to identify potential therapeutic biomarkers for atherosclerosis by analyzing the gene expression profiles of macrophages incubated with total lipoproteins. The microarray dataset no. GSE84791 obtained from Gene Expression Omnibus (GEO) database was used for this study. In the comparison of two groups: (i) THP-1 macrophage models incubated with non-LPL hydrolysed products and (ii) LPL hydrolysed products, a total of 283 differentially expressed genes (DEGs) were identified. The Gene Ontology (GO) analysis indicated that the upregulated DEGs gene set were mainly enriched in cellular response to inflammation, stress, substance uptake and intracellular transport. Besides, upregulated DEGs were significantly enriched in PPAR signalling pathway by the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Notably, GO analysis revealed that the downregulated DEGs were mainly enriched in cellular proliferation, while the KEGG analysis showed that the gene set was significantly enriched in cell cycle process. The top 10 hub genes including KIF2C, NCAPG, BUB1, TOP2A, CENPF, TTK, CCNA2, PLK4, CDC6, and KIF11, was identified from the Protein-Protein Interaction (PPI) network, which constructed using STRING and further analysed using the Network Analyzer, MCODE and cytoHubba. The present study indicated that the downregulation of these genes which involved in the process of cell cycle may have an implication on atherosclerosis development.