Neutrophils incite and macrophages avert electrical storm after myocardial infarction.

Autor: Grune J; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Lewis AJM; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; These authors contributed equally and are listed in alphabetical order: Andrew J. M. Lewis, Masahiro Yamazoe., Yamazoe M; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; These authors contributed equally and are listed in alphabetical order: Andrew J. M. Lewis, Masahiro Yamazoe., Hulsmans M; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Rohde D; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Xiao L; Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Zhang S; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Ott C; DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany.; Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany., Calcagno DM; Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA., Zhou Y; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Timm K; Department of Pharmacology, University of Oxford, Oxford, UK., Shanmuganathan M; Radcliffe Department of Medicine, University of Oxford, Oxford, UK.; National Institute for Health (NIHR) Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, UK., Pulous FE; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Schloss MJ; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Foy BH; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Department of Pathology, Massachusetts General Hospital, Boston, MA, USA., Capen D; Program in Membrane Biology, Nephrology Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Vinegoni C; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Wojtkiewicz GR; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Iwamoto Y; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Grune T; DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany.; Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany., Brown D; Program in Membrane Biology, Nephrology Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Higgins J; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Department of Pathology, Massachusetts General Hospital, Boston, MA, USA., Ferreira VM; Radcliffe Department of Medicine, University of Oxford, Oxford, UK., Herring N; National Institute for Health (NIHR) Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, UK.; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK., Channon KM; Radcliffe Department of Medicine, University of Oxford, Oxford, UK.; National Institute for Health (NIHR) Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, UK., Neubauer S; Radcliffe Department of Medicine, University of Oxford, Oxford, UK.; National Institute for Health (NIHR) Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, UK., Sosnovik DE; Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Milan DJ; Leducq Foundation, Boston, MA, USA., Swirski FK; Cardiovascular Research Institute and Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA., King KR; Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA.; Department of Medicine, Division of Cardiovascular Medicine, University of California, San Diego La Jolla, CA, USA., Aguirre AD; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Ellinor PT; Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.; The Broad Institute of MIT and Harvard, Cambridge, MA, USA., Nahrendorf M; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Department of Internal Medicine, University Hospital Wuerzburg, Wuerzburg, Germany.
Jazyk: angličtina
Zdroj: Nature cardiovascular research [Nat Cardiovasc Res] 2022 Jul; Vol. 1 (7), pp. 649-664. Date of Electronic Publication: 2022 Jul 11.
DOI: 10.1038/s44161-022-00094-w
Abstrakt: Sudden cardiac death, arising from abnormal electrical conduction, occurs frequently in patients with coronary heart disease. Myocardial ischemia simultaneously induces arrhythmia and massive myocardial leukocyte changes. In this study, we optimized a mouse model in which hypokalemia combined with myocardial infarction triggered spontaneous ventricular tachycardia in ambulatory mice, and we showed that major leukocyte subsets have opposing effects on cardiac conduction. Neutrophils increased ventricular tachycardia via lipocalin-2 in mice, whereas neutrophilia associated with ventricular tachycardia in patients. In contrast, macrophages protected against arrhythmia. Depleting recruited macrophages in Ccr2 -/- mice or all macrophage subsets with Csf1 receptor inhibition increased both ventricular tachycardia and fibrillation. Higher arrhythmia burden and mortality in Cd36 -/- and Mertk -/- mice, viewed together with reduced mitochondrial integrity and accelerated cardiomyocyte death in the absence of macrophages, indicated that receptor-mediated phagocytosis protects against lethal electrical storm. Thus, modulation of leukocyte function provides a potential therapeutic pathway for reducing the risk of sudden cardiac death.
Competing Interests: Competing interests J.G. and M.N. filed an invention disclosure on the STORM model. M.N. has received funds or material research support from Alnylam, Biotronik, CSL Behring, GlycoMimetics, GlaxoSmithKline, Medtronic, Novartis and Pfizer as well as consulting fees from Eli Lilly, Biogen, Gimv, IFM Therapeutics, Molecular Imaging, Sigilon and Verseau Therapeutics. P.T.E. has received sponsored research support from Bayer AG and IBM Health and has consulted for Bayer AG, Novartis and MyoKardia. A.D.A. has received sponsored research support from Amgen and Philip Research. The other authors declare no competing interests.
Databáze: MEDLINE
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