SDC2 May Be A Key Gene In The Process Of Monocyte To Macrophage Differentiation In Acute Coronary Syndrome

Objective: The aim of this study is to explore the key genes,biological functions and possible signaling pathways in the process of monocyte to macrophage differentiation in acute coronary syndrome(ACS),to explore the potential molecular mechanisms and to find possible gene therapy targets.Methods: We downloaded a microarray dataset GSE10220 from the Gene Expression Omnbus Database(GEO),which contains Gene Expression information of monocytes and macrophages in the blood of patients with ACS.Then,in R software,LIMMA software package was used to analyze the gene expression matrix,and then the desired differential gene(DEG)was obtained by screening the genes according to the criteria of corrected P value less than 0.01 and Log Fc ≥2.0.Whereafter,we conducted Ontology Function Enrichment Analysis(GO)and Kyoto Encyclopedia of Genes and Genomes Analysis(KEGG)on the David website to understand the biological processes,cell composition,molecular functions and signaling pathways of differential genes.At the same time,we also used the String website uploaded by DEG to construct the PPI network map,and then found the key modules in PPI in Cytoscape.Finally,genes in key modules were selected for cell validation using RT-PCR technology.Results:Bioinformatics was used to screen out 226 differential genes,including 149up-regulated genes and 77 down-regulated genes.After GO and KEGG analysis of these 226 differential genes,we found that these DEGs are widely involved in biological processes such as inflammatory response and lipid metabolism in the body.After that,PPI graph was constructed,and Cytoscape software was used to determine a key module including SDC2,VWA1,SPP1,APOA2,APOE,F5,VCAN and SERPINA1.In addition,by exploring the interaction between key genes and drugs,we found that there is no relevant gene targeting drug at present.Finally,we selected SDC2 for experimental verification,and in the process of M-CSF induction of THP-1cells,it was found that the expression of SDC2 gradually increased with the increase of time.Conclusions: SDC2 may be involved in the occurrence and development of inflammation in ACS and regulate the differentiation process of monocytes to macrophages.