Background: Lipid infiltration and inflammatory response run through the occurrence of atherosclerosis. Differentiation into macrophages and foam cell formation are the key steps of AS. Aim of this study was that the differential gene expression between foam cells and macrophages was analyzed to search the key links of foam cell generation, so as to explore the pathogenesis of atherosclerosis and provide targets for the early screening and prevention of coronary artery disease (CAD).
Methods: The gene expression profiles of GSE9874 were downloaded from Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE9874) on GPL96 [HG-U133A] Affymetrix Human Genome U133. A total of 22,383 genes were analyzed for differentially expression genes (DEGs) by Bayes package. GO enrichment analysis and KEGG pathway analysis for DEGs were performed using KOBAS 3.0 software (Peking University, Beijing, China). STRING software (STRING 10.0; European Molecular Biology Laboratory, Heidelberg, Germany) was used to analyze the protein-protein interaction (PPI) of DEGs.
Results: A total of 167 DEGs between macrophages and foam cells were identified. Compared with macrophages, 102 genes were significantly upregulated and 65 genes were significantly downregulated (P < 0.01, fold-change > 1) in foam cells. DEGs were mainly enrich in 'sterol biosynthetic and metabolic process', 'cholesterol metabolic and biosynthetic process' by GO enrichment analysis. The results of KEGG pathway analysis showed all differential genes are involved in biological processes through 143 KEGG pathways. A PPI network of the DEGs was constructed and 10 outstanding genes of the PPI network was identified by using Cytoscape, which include HMGCR, SREBF2, LDLR, HMGCS1, FDFT1, LPL, DHCR24, SQLE, ABCA1 and FDPS.
Conclusion: Lipid metabolism related genes and molecular pathways were the key to the transformation of macrophages into foam cells. Therefore, lipid metabolism disorder is the key to turn macrophages into foam cells, which plays a major role in CAD.
Keywords: Differential expression gene; Foam cell; GO enrichment; KEGG pathway analysis; Macrophages; Protein interaction network.