{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:59:22Z","timestamp":1790189962081,"version":"4.1.0"},"reference-count":14,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2026,7]]},"abstract":"\n BACKGROUND:<\/jats:title>\n Atherosclerotic plaque destabilization is promoted by inflammatory cell recruitment, tissue cell death, and mechanical weakening. Neutrophils drive vascular tissue injury and perpetuate inflammation and represent a viable therapeutic opportunity. Here, we identify a distinct subset of activated neutrophils within atherosclerotic lesions that express the chemokine receptor CCR2 (C-C chemokine receptor type 2), which directs their migration toward areas enriched with smooth muscle cells and contributes to plaque instability.<\/jats:p>\n <\/jats:sec>\n \n METHODS:<\/jats:title>\n \n Flow cytometry and single-cell transcriptomic analysis of CCR2\n +<\/jats:sup>\n neutrophils within murine and human atherosclerotic plaques. Tracking of CCR2\n +<\/jats:sup>\n neutrophil in hypercholesterolemic\n Ldlr<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n mice and in mice reconstituted with\n Ccr2<\/jats:italic>\n \n GFP\/<\/jats:italic>\n <\/jats:sup>\n \n \u2212<\/jats:italic>\n <\/jats:sup>\n bone marrow. In vivo reactive oxygen species and neutrophil extracellular trap analysis in lipopolysaccharide-induced peritonitis. In vitro migration assays of neutrophils deficient for or treated with a specific antagonist against chemokine receptors. In vivo neutrophil recruitment and features of atherosclerotic plaque vulnerability analysis on CCR2 and CCL2 (C-C motif chemokine ligand 2) blockade in a model of advanced atherosclerosis in\n Apoe<\/jats:italic>\n \n \u2212\/<\/jats:italic>\n <\/jats:sup>\n \n \u2212<\/jats:italic>\n <\/jats:sup>\n mice.\n <\/jats:p>\n <\/jats:sec>\n \n RESULTS:<\/jats:title>\n \n CCR2\n +<\/jats:sup>\n neutrophils preferentially populate mouse and human atherosclerotic lesions and display a proinflammatory phenotype with enhanced capacity for reactive oxygen species production and neutrophil extracellular trap release. Genetic or pharmacological CCR2 inhibition reduced neutrophil migration and infiltration to the atherosclerotic lesion, reducing their presence in smooth muscle cell\u2013rich areas. Consistently, neutralization of the CCR2 ligand CCL2 decreased lesional neutrophil numbers and preserved fibrous cap integrity by increasing smooth muscle cell content and decreasing features associated with plaque instability.\n <\/jats:p>\n <\/jats:sec>\n \n CONCLUSIONS:<\/jats:title>\n Our data suggest that a subset of CCR2-expressing neutrophils senses smooth muscle cell\u2013derived CCR2 ligands to infiltrate and promote vulnerable atherosclerotic lesions. These results support that neutrophil functional heterogeneity within the atherosclerotic lesions alters lesion stability. Specific targeting thereof may improve plaque stability without impacting host defense.<\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/atvbaha.126.324654","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T09:00:43Z","timestamp":1778749243000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["CCR2\n +<\/sup>\n Neutrophils Exhibit a Proinflammatory Phenotype and Contribute to Plaque Vulnerability"],"prefix":"10.1161","volume":"46","author":[{"given":"Merieme","family":"Farjia","sequence":"first","affiliation":[{"name":"Institute of Experimental Pathology (ExPat), Center for Molecular Biology of Inflammation (ZMBE), University of M\u00fcnster, Germany (M.F., C.P., L.M.V., R.C., M.M., O.S., C.S.-R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Pan","sequence":"additional","affiliation":[{"name":"Institute of Experimental Pathology (ExPat), Center for Molecular Biology of Inflammation (ZMBE), University of M\u00fcnster, Germany (M.F., C.P., L.M.V., R.C., M.M., O.S., C.S.-R.)."},{"name":"East Hospital Affiliated to Tongji University, Shanghai, China (C.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quinte","family":"Braster","sequence":"additional","affiliation":[{"name":"Biolegend, Amsterdam, the Netherlands (Q.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Lemnitzer","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Cancer Immunology, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Germany (P.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8031-017X","authenticated-orcid":true,"given":"Nadja","family":"Sachs","sequence":"additional","affiliation":[{"name":"Department of Vascular and Endovascular Surgery (N.S.), Technical University Munich, Germany."},{"name":"German Centre for Cardiovascular Research, Munich (N.S., C.S., L.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3323-1884","authenticated-orcid":true,"given":"Lina Marie","family":"V\u00f6cking","sequence":"additional","affiliation":[{"name":"Institute of Experimental Pathology (ExPat), Center for Molecular Biology of Inflammation (ZMBE), University of M\u00fcnster, Germany (M.F., C.P., L.M.V., R.C., M.M., O.S., C.S.-R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7564-2919","authenticated-orcid":true,"given":"Raphael","family":"Chevre","sequence":"additional","affiliation":[{"name":"Institute of Experimental Pathology (ExPat), Center for Molecular Biology of Inflammation (ZMBE), University of M\u00fcnster, Germany (M.F., C.P., L.M.V., R.C., M.M., O.S., C.S.-R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9754-2399","authenticated-orcid":true,"given":"Mariano","family":"Malamud","sequence":"additional","affiliation":[{"name":"Institute of Experimental Pathology (ExPat), Center for Molecular Biology of Inflammation (ZMBE), University of M\u00fcnster, Germany (M.F., C.P., L.M.V., R.C., M.M., O.S., C.S.-R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8149-0747","authenticated-orcid":true,"given":"Christian","family":"Schulz","sequence":"additional","affiliation":[{"name":"German Centre for Cardiovascular Research, Munich (N.S., C.S., L.M.)."},{"name":"Department of Medicine I, Ludwig Maximilian University Hospital, Ludwig Maximilian University Munich, Germany (C.S.)."},{"name":"Department of Immunopharmacology, Mannheim Institute for Innate Immunoscience, Medical Faculty Mannheim, Heidelberg University, Germany (C.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5228-2634","authenticated-orcid":true,"given":"Lars","family":"Maegdefessel","sequence":"additional","affiliation":[{"name":"Institute of Molecular Vascular Medicine, TUM Klinikum rechts der Isar (L.M.), Technical University Munich, Germany."},{"name":"German Centre for Cardiovascular Research, Munich (N.S., C.S., L.M.)."},{"name":"Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden (L.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7854-0694","authenticated-orcid":true,"given":"Oliver","family":"Soehnlein","sequence":"additional","affiliation":[{"name":"Institute of Experimental Pathology (ExPat), Center for Molecular Biology of Inflammation (ZMBE), University of M\u00fcnster, Germany (M.F., C.P., L.M.V., R.C., M.M., O.S., C.S.-R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1169-7475","authenticated-orcid":true,"given":"Carlos","family":"Silvestre-Roig","sequence":"additional","affiliation":[{"name":"Institute of Experimental Pathology (ExPat), Center for Molecular Biology of Inflammation (ZMBE), University of M\u00fcnster, Germany (M.F., C.P., L.M.V., R.C., M.M., O.S., 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