Abstract
BackgroundLipid 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).MethodsThe 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.ResultsA 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.
Highlights
Lipid infiltration and inflammatory response run through the occurrence of atherosclerosis
Protein interaction network analysis A protein-protein interaction (PPI) network of the differentially expression genes (DEGs) was constructed (Fig. 6), and 10 outstanding genes of the PPI network was identified by using Cytoscape (Fig. 7), which include HMGCR, SREBF2, HMGCS1, LDL receptor (LDLR), Farnesyl diphosphate farnesyl transferase 1 (FDFT1), Lipoprotein lipase (LPL), Squalene epoxidase (SQLE), 3β-hydroxysterol Δ24reductase (DHCR24), ATP-binding cassette A1 (ABCA1) and Farnesyl diphosphate synthase (FDPS)
The results of this study showed that the differential genes mainly regulated the transformation of macrophages into foam cells by up-regulating and downregulating the sterol biosynthetic and metabolic process, and the cholesterol metabolic and biosynthetic process
Summary
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). Song et al BMC Cardiovascular Disorders (2020) 20:211 and differentiation into macrophages, foam cell formation, proteolysis, apoptosis, angiogenesis are the key steps of AS [3]. Each of these mechanisms and potential diagnostic and therapeutic targets have been extensively studied. The mechanism of CAD has not been fully elucidated
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