α1AMPK deletion in myelomonocytic cells induces a pro-inflammatory phenotype and enhances angiotensin II-induced vascular dysfunction
| Autor: | Marc Foretz, Moritz Brandt, Eberhard Schulz, Philip Wenzel, Matthias Oelze, John F. Keaney, Swenja Kröller-Schön, Thomas Münzel, Benoit Viollet, Thomas Jansen, Andreas Daiber, Sebastian Steven, Jeremy Lagrange, Miroslava Kvandova, Sanela Kalinovic, Tanja Schönfelder |
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| Přispěvatelé: | Johannes Gutenberg - Universität Mainz (JGU), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), University of Massachusetts Medical School [Worcester] (UMASS), University of Massachusetts System (UMASS), Johannes Gutenberg - University of Mainz (JGU) |
| Rok vydání: | 2018 |
| Předmět: |
MESH: Signal Transduction
0301 basic medicine CCR2 Physiology medicine.medical_treatment MESH: Aortic Diseases AMP-Activated Protein Kinases 030204 cardiovascular system & hematology MESH: Mice Knockout 0302 clinical medicine MESH: Animals MESH: AMP-Activated Protein Kinases Aorta Cells Cultured Mice Knockout MESH: Cytokines MESH: Oxidative Stress biology Chemistry Angiotensin II MESH: Genetic Predisposition to Disease MESH: Aorta [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biomolecules [q-bio.BM] Respiratory burst Vasodilation Phenotype Cytokine Cytokines Tumor necrosis factor alpha MESH: Angiotensin II Inflammation Mediators medicine.symptom Cardiology and Cardiovascular Medicine Signal Transduction MESH: Cells Cultured MESH: Inflammation Mediators Aortic Diseases Inflammation MESH: Phenotype MESH: Vasodilation 03 medical and health sciences Immune system MESH: Mice Inbred C57BL Physiology (medical) medicine Animals Genetic Predisposition to Disease [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biochemistry [q-bio.BM] Interleukin 6 Macrophages MESH: Macrophages [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology Mice Inbred C57BL Disease Models Animal Oxidative Stress 030104 developmental biology MESH: Gene Deletion Cancer research biology.protein MESH: Disease Models Animal Gene Deletion |
| Zdroj: | Cardiovascular Research Cardiovascular Research, Oxford University Press (OUP), 2018, 114 (14), pp.1883-1893. ⟨10.1093/cvr/cvy172⟩ |
| ISSN: | 1755-3245 0008-6363 |
| DOI: | 10.1093/cvr/cvy172 |
| Popis: | Aims Immune cell function involves energy-dependent processes including growth, proliferation, and cytokine production. Since the AMP-activated protein kinase (AMPK) is a crucial regulator of intracellular energy homeostasis, its expression and activity may also affect innate and adaptive immune cell responses. Therefore, we aimed to investigate the consequences of α1AMPK deletion in myelomonocytic cells on vascular function, inflammation, and hypertension during chronic angiotensin II (ATII) treatment. Methods and results We generated a mouse strain with α1AMPK deletion in lysozyme M+ myelomonocytic cells. Compared to controls, chronic ATII infusion (1 mg/kg/day for 7 days) lead to increased vascular oxidative stress and aggravated endothelial dysfunction in LysM-Cre+ x α1AMPKfl/fl mice. This was accompanied by an increased aortic infiltration of CD11b+F4/80+ macrophages and enhanced pro-inflammatory cytokine release (tumour necrosis factor-alpha, interferon-gamma, and interleukin-6). Mechanistically, we found that increased expression of C-C chemokine receptor 2 (CCR2) in α1AMPK deficient myelomonocytic cells facilitated their recruitment to the vascular wall. In addition, expression of the ATII receptor type 1a and the oxidative burst was increased in these cells, indicating an increased susceptibility towards pro-oxidant stimuli. Conclusions In summary, α1AMPK deletion in myelomonocytic cells aggravates vascular oxidative stress and dysfunction by enhancing their recruitment to the vascular wall and increasing their susceptibility towards pro-oxidant stimuli. Our observations suggest that metabolic control in myelomonocytic cells has profound implications for their inflammatory phenotype and may trigger the development of vascular disease. |
| Databáze: | OpenAIRE |
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