Myeloid cell-derived interleukin-6 induces vascular dysfunction and vascular and systemic inflammation
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Le résumé fourni par la source
Abstract Aims The cytokine interleukin-6 (IL-6) plays a central role in the inflammation cascade as well as cardiovascular disease progression. Since myeloid cells are a primary source of IL-6 formation, we aimed to generate a mouse model to study the role of myeloid cell-derived IL-6 in vascular disease. Methods and results Interleukin-6-overexpressing (IL-6OE) mice were generated and crossed with LysM-Cre mice, to generate mice (LysM-IL-6OE mice) overexpressing the cytokine in myeloid cells. Eight- to 12-week-old LysM-IL-6OE mice spontaneously developed inflammatory colitis and significantly impaired endothelium-dependent aortic relaxation, increased aortic reactive oxygen species (ROS) formation, and vascular dysfunction in resistance vessels. The latter phenotype was associated with decreased survival. Vascular dysfunction was accompanied by a significant accumulation of neutrophils, monocytes, and macrophages in the aorta, increased myeloid cell reactivity (elevated ROS production), and vascular fibrosis associated with phenotypic changes in vascular smooth muscle cells. In addition to elevated Mcp1 and Cxcl1 mRNA levels, aortae from LysM-IL-6OE mice expressed higher levels of inducible NO synthase and endothelin-1, thus partially accounting for vascular dysfunction, whereas systemic blood pressure alterations were not observed. Bone marrow (BM) transplantation experiments revealed that vascular dysfunction and ROS formation were driven by BM cell-derived IL-6 in a dose-dependent manner. Conclusion Mice with conditional overexpression of IL-6 in myeloid cells show systemic and vascular inflammation as well as endothelial dysfunction. A decrease in circulating IL-6 levels by replacing IL-6-producing myeloid cells in the BM improved vascular dysfunction in this model, underpinning the relevant role of IL-6 in vascular disease.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Myeloid cell-derived interleukin-6 induces vascular dysfunction and vascular and systemic inflammation
- Date Crossref
- 12/06/2024
- Éditeur
- Oxford University Press (OUP)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Johannes Gutenberg University Mainz Department of Cardiology—Cardiology I pays non établi dans la noticeUniversité ou école supérieure
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University Medical Center of the Johannes Gutenberg University Mainz Institute of Neuroradiology pays non établi dans la noticeÉtablissement de santé
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German Centre for Cardiovascular Research pays non établi dans la noticeStructure de recherche
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National and Kapodistrian University of Athens pays non établi dans la noticeUniversité ou école supérieure
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Leipzig University pays non établi dans la noticeUniversité ou école supérieure
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Heidelberg University pays non établi dans la noticeUniversité ou école supérieure
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University Hospital Heidelberg Department of Dermatology pays non établi dans la noticeÉtablissement de santé
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Goethe University Frankfurt Institute for Vascular Signalling pays non établi dans la noticeUniversité ou école supérieure
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Max Planck Institute for Metabolism Research pays non établi dans la noticeStructure de recherche
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University of Tübingen pays non établi dans la noticeUniversité ou école supérieure
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Boston University Department of Medicine pays non établi dans la noticeUniversité ou école supérieure
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University Medical Center Mainz Center for Thrombosis and Hemostasis (CTH) pays non établi dans la noticeUniversité ou école supérieure
Department of Cardiology—Cardiology I — Johannes Gutenberg University Mainz, Institute of Neuroradiology — University Medical Center of the Johannes Gutenberg University Mainz et German Centre for Cardiovascular Research, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.