{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:55:28Z","timestamp":1790618128909,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Cell Communication and Signaling"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Atherosclerotic plaque progression is shaped by coordinated inflammatory and remodeling programs involving immune cells and vascular wall cells. Inflammatory macrophage activation and vascular smooth muscle cell (VSMC) phenotypic remodeling are central features of human atherosclerosis, but their transcriptomic relationships during plaque progression remain incompletely characterized. This study integrated single\u2010cell and bulk transcriptomic datasets to examine highly inflammatory macrophage states, VSMC remodeling\u2010related transcriptional programs, and candidate ligand\u2010receptor expression patterns in human atherosclerotic plaques. Human atherosclerotic plaque single\u2010cell RNA sequencing data from GSE260657 and bulk transcriptomic data from GSE28829 were analyzed. After quality control, 7628 cells were retained for single\u2010cell analysis. Major cell types were annotated using canonical markers, followed by reclustering of macrophages and VSMC\u2010related cells. Functional module scoring, differential expression analysis, Gene Ontology biological process enrichment, and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to characterize macrophage transcriptional states. Slingshot was applied to infer VSMC pseudotime ordering. CellChat and NicheNet were used to prioritize candidate ligand\u2010receptor expression patterns and ligand\u2010associated VSMC target gene programs. External bulk transcriptomic analysis was performed to examine whether single\u2010cell\u2010derived inflammatory and remodeling signatures were represented at the tissue\u2010transcriptome level during plaque progression. Macrophage reclustering identified a highly inflammatory macrophage state characterized by prominent inflammatory activation, cytokine\u2010response, and stress\u2010response features. Genes upregulated in this population were enriched in pathways related to tumor necrosis factor (TNF) response, nuclear factor kappa B signaling, leukocyte activation, cytokine signaling, lipid and atherosclerosis, toll\u2010like receptor signaling, and inflammasome\u2010associated inflammation. VSMC reclustering revealed contractile VSMCs, PTHLH+\u00a0synthetic VSMCs, KRT7+ VSMC\u2010like cells, interferon\u2010responsive VSMCs, pericyte\u2010like mural cells, and osteogenic\/modulated VSMCs. Pseudotime analysis showed a broad contractile\u2010to\u2010osteogenic\/modulated transcriptional continuum accompanied by increased expression of remodeling\u2010associated genes and selected inflammatory or remodeling\u2010associated receptor genes. CellChat and NicheNet analyses prioritized candidate ligand\u2010receptor and ligand\u2010associated target gene expression patterns involving SPP1\u2013CD44, TNF\u2013TNFRSF1A, IL1B\u2013IL1R1\/IL1RAP, MIF\u2013ACKR3, PDGFB\u2013PDGFRB, and FN1\u2013SDC1\/ITGB1. In GSE28829, inflammatory macrophage\u2010, osteogenic\/modulated VSMC\u2010, candidate ligand\u2010receptor expression\u2010, SPP1\u2013CD44 candidate axis\u2010, and NicheNet\u2010prioritized target program\u2010related signatures were more prominent in advanced plaques and were positively correlated with each other. This integrative transcriptomic analysis identified a highly inflammatory macrophage state and a VSMC remodeling continuum in human atherosclerotic plaques. Candidate ligand\u2010receptor and ligand\u2010associated target gene expression patterns linked inflammatory macrophage activation with osteogenic\/modulated VSMC remodeling at the computational level. External bulk data further showed coordinated enrichment of inflammatory and remodeling signatures in advanced plaques. These findings provide a descriptive and hypothesis\u2010generating transcriptomic framework for understanding inflammatory macrophage activation and VSMC remodeling in human atherosclerosis.<\/jats:p>","DOI":"10.1002\/ccs3.70106","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T16:39:32Z","timestamp":1788453572000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Coordinated inflammatory macrophage and vascular smooth muscle cell remodeling signatures in human atherosclerosis: An integrative single\u2010cell and bulk transcriptomic analysis"],"prefix":"10.1002","volume":"20","author":[{"given":"Xinyu","family":"Dong","sequence":"first","affiliation":[{"name":"Department of Vascular Surgery the First Affiliated Hospital of Harbin Medical University  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuesong","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The Sixth Affiliated Hospital of Harbin Medical University  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science and Technology Harbin Medical University Daqing  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5689-3475","authenticated-orcid":false,"given":"Yuhao","family":"Dong","sequence":"additional","affiliation":[{"name":"Harbin Medical University  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Xuan","sequence":"additional","affiliation":[{"name":"Department of Breast and Vascular Surgery Harbin the First Hospital  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muning","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery the First Affiliated Hospital of Harbin Medical University  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyao","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery Harbin Fifth Hospital  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyi","family":"Lu","sequence":"additional","affiliation":[{"name":"School of Public Health Harbin Medical University  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4509-2119","authenticated-orcid":false,"given":"Zhiyang","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery the First Affiliated Hospital of Harbin Medical University  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572\u2010019\u20100106\u2010z"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569\u2010019\u20100227\u20109"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvab046"},{"issue":"13","key":"e_1_2_12_5_1","first-page":"2525","article-title":"Inflammation During the Life Cycle of the Atherosclerotic Plaque","volume":"117","author":"Libby P.","year":"2021","journal-title":"Cardiovascular 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Expression Profile Analysis of the Progression of Carotid Atherosclerotic Plaques","volume":"17","author":"Liu W.","year":"2018","journal-title":"Molecular Medicine Reports"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/4323496"}],"container-title":["Journal of Cell Communication and 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