Identification\nof Macrophage-Associated Novel Drug\nTargets in Atherosclerosis Based on Integrated Transcriptome Features

Background: This study explores the pathological mechanisms\nof\natherosclerosis (AS), focusing on the role of macrophages in its formation\nand development, and potential therapeutic targets. Methods: The heterogeneity\nof the AS single-cell data set GSE131778 was analyzed using Seurat.\nTissue sequencing data GSE28829 and GSE43292 were analyzed for immune\ncell abundance using CIBERSORT. Differential genes were identified,\nand WGCNA was used to create a coexpression network. Hub genes were\nidentified using MCODE and CytoHubba and analyzed with GO and KEGG\nenrichment analysis, GSVA, and immune infiltration analysis. DrugBank\nidentified potential drugs, and molecular docking verified drug binding\nto key targets. Key targets were experimentally validated. Results:\nNineteen cell clusters were identified in the GSE131778 data set,\nclassified into ten cell types. Macrophages in AS and normal tissues\nwere identified based on cell abundance. CIBERSORT showed a significant\nincrease in cell cluster 9 in AS samples. Thirty-two hub genes, including\nCD86, LILRB2, and IRF8, were validated. GO and KEGG analyses indicated\nHub genes primarily affect immune functions. GSVA identified 29 significantly\nincreased pathways in AS samples. Immune infiltration analysis revealed\na positive correlation between IRF8, CD86, and LILRB2 expression and\nmacrophage content. Molecular docking suggested CD86 as a potential\ndrug target for AS. qRT-PCR confirmed increased IRF8 and CD86 expression.\nConclusions: CD86, LILRB2, and IRF8 are highly expressed in foam cell\nsamples, with CD86 forming hydrogen bonds with several AS drugs, indicating\nCD86 as a promising target for AS treatment.