CCR2+ neutrophils exhibit a proinflammatory phenotype and contribute to plaque vulnerability
BACKGROUND: - 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...
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| Autori principali: | , , , , , , , , , , , |
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| Natura: | Article (Journal) |
| Lingua: | inglese |
| Pubblicazione: |
14 May 2026
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| In: |
Arteriosclerosis, thrombosis, and vascular biology
Year: 2026, Volume: 46, Fascicolo: 7 |
| ISSN: | 1524-4636 |
| DOI: | 10.1161/ATVBAHA.126.324654 |
| Accesso online: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1161/ATVBAHA.126.324654 Verlag, lizenzpflichtig, Volltext: https://www.ahajournals.org/doi/10.1161/ATVBAHA.126.324654 
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| Note sull'autore: | Merieme Farjia, Chang Pan, Quinte Braster, Patricia Lemnitzer, Nadja Sachs, Lina Marie Vöcking, Raphael Chevre, Mariano Malamud, Christian Schulz, Lars Maegdefessel, Oliver Soehnlein, and Carlos Silvestre-Roig |
| Riassunto: | BACKGROUND: - 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. - METHODS: - Flow cytometry and single-cell transcriptomic analysis of CCR2+ neutrophils within murine and human atherosclerotic plaques. Tracking of CCR2+ neutrophil in hypercholesterolemic Ldlr−/− mice and in mice reconstituted with Ccr2GFP/− 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 Apoe−/− mice. - RESULTS: - CCR2+ 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-rich 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. - CONCLUSIONS: - Our data suggest that a subset of CCR2-expressing neutrophils senses smooth muscle cell-derived 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. |
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| Descrizione del documento: | Im Titel ist das Plus-Symbol hochgestellt Gesehen am 06.08.2026 |
| Descrizione fisica: | Online Resource |
| ISSN: | 1524-4636 |
| DOI: | 10.1161/ATVBAHA.126.324654 |