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This study aimed to investigate the diversity of EDs using single\u2010cell ribonucleic acid sequencing (scRNA\u2010seq) and to evaluate the regulation of intercellular adhesion molecule 1 (ICAM1) on the ferroptosis\u2010related protein, prostaglandin\u2010endoperoxide synthase 2 (PTGS2), in CAP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methodology<\/jats:title><jats:p>EDs from the uploaded scRNA\u2010seq data of five CAP samples (GSE181688 and GSE197680) were categorized using distinct marker genes. The interactions between vein EDs (veinEndo) and other cell types were analysed using CellPhoneDB. Differentially expressed proteins in the proteomics of human umbilical vein EDs (HUVECs) and THP\u20101\u2010derived macrophages infected with <jats:italic>Porphyromonas gingivalis<\/jats:italic> were compared with the differentially expressed genes (DEGs) of VeinEndo in scRNA\u2010seq of CAP versus healthy control periodontal tissues. The protein\u2013protein interaction of ICAM1\u2013PTGS2 in macrophages and HUVECs was validated by adding recombinant ICAM1, ICAM1 inhibitor and PTGS2 inhibitor using real\u2010time polymerase chain reaction (PCR), western blotting, and immunofluorescence staining.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>EDs in patients with CAP were divided into eight subclusters: five vein ED, capillaries, arterials and EC (PLA). There were 29 mutually upregulated DEGs and two mutually downregulated DEGs in vein cells in the scRNA\u2010seq data, as well as differentially expressed proteins in the proteomics of HUVECs. Real\u2010time PCR and immunofluorescence staining showed that ICAM1 and PTGS2 were highly expressed in CAP, infected HUVECs, and macrophages. Recombinant protein ICAM1 may improve PTGS2 expression, reactive oxygen species (ROS), and Fe<jats:sup>2+<\/jats:sup> levels and decrease glutathione peroxidase 4 (GPX4) and SLC7A11 protein levels. ICAM1 inhibitor may inverse the above changes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>scRNA\u2010seq revealed the diversity of EDs in CAP and identified the possible regulation of ICAM1 by the ferroptosis\u2010related protein, PTGS2, in infected HUVECs and macrophages, thus providing a basis for therapeutic approaches that target the inflammatory microenvironment of CAP.<\/jats:p><\/jats:sec>","DOI":"10.1111\/iej.14080","type":"journal-article","created":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T15:14:36Z","timestamp":1715094876000},"page":"1228-1246","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Integration of single\u2010cell <scp>RNA<\/scp> sequencing of endothelial cells and proteomics to unravel the role of <scp>ICAM1<\/scp>\u2013<scp>PTGS2<\/scp> communication in apical periodontitis: A laboratory 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