Bioinformatics Analysis Of The Mechanism Of The Chemokine Regulating Macrophage Polarization In Atherosclerosis

Objective:Atherosclerosis(AS)is a systemic disease involving multiple blood vessels and is one of the major causes of cardiovascular disease for which there is no effective treatment.Among them,macrophages play a central role in the development of AS.Chemokines,the main mediators of macrophage chemotaxis,play a key role in the immune and inflammatory response.The role and mechanisms of chemokines in AS are currently unknown.Therefore,the aim of this study is to investigate the role and mechanism of chemokines in AS initially using bioinformatics technology.Methods:In this study,chemokine ligands and receptors were obtained by mining public databases(NCBI-GEO database,ArrayExpress database and single-cell RNA sequencing(scRNA-seq)database)and an extensive literature search.The expression levels of chemokines in mouse tissues were analyzed by ArrayExpress using metascape software for signaling pathway enrichment,scRNA-seq data for chemokine expression in AS plaque progression and regression,and GEO2R for chemokine expression during macrophage polarization;Using Ingenuity Pathway Analysis(IPA)software,we analyzed regulatory factors such as transcription factors(TFs)and microRNAs(miRNAs)that are significantly differentially expressed upstream of chemokines in macrophage polarization.Finally,a model of chemokine regulation of AS was established based on the above results.Results:In this study,65 chemokine genes and 20 chemokine enrichment signaling pathways were screened.Through bioinformatics analysis,we have five main findings:1)Chemokines are differentially expressed in mouse macrophages derived from different tissues.2)Chemokines promote the polarization of primary macrophages into M1-,M2a-,and M2b-type macrophages.3)TFs and miRNAs can modulate macrophage polarization by regulating chemokines.4)Chemokines are differentially expressed in the progression and regression of AS.5)Two sets of hypothetical molecular signaling models were developed.The first model describes the mechanisms of chemokine-mediated transcriptional regulation of macrophage polarization.The second model summarizes the potential molecular mechanisms underlying chemokine regulation of AS.conclusions:1.The goal of treating AS can be achieved by regulating chemokine and regulating the polarization of macrophages.2.Chemokine CCL4,CCL5,CCL8,CCL19,CXCL3,CXCL10,CXCL13 and CCR7 may play a key role in the progression and regression of AS.