Neutrophils incite and macrophages avert electrical storm after myocardial infarction
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 m...
| Главные авторы: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Формат: | Journal article |
| Язык: | English |
| Опубликовано: |
Springer Nature
2022
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| Предметы: |
| _version_ | 1826310953116893184 |
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| author | Grune, J Lewis, AJM Yamazoe, M Hulsmans, M Rohde, D Xiao, L Zhang, S Ott, C Calcagno, DM Zhou, Y Timm, K Shanmuganathan, M Pulous, FE Schloss, MJ Foy, BH Capen, D Vinegoni, C Wojtkiewicz, GR Iwamoto, Y Grune, T Brown, D Higgins, J Ferreira, VM Herring, N Channon, KM Neubauer, S Sosnovik, DE Milan, DJ Swirski, FK King, KR Aguirre, AD Ellinor, PT Nahrendorf, M |
| author2 | Oxford Acute Myocardial Infarction (OxAMI) Study |
| author_facet | Oxford Acute Myocardial Infarction (OxAMI) Study Grune, J Lewis, AJM Yamazoe, M Hulsmans, M Rohde, D Xiao, L Zhang, S Ott, C Calcagno, DM Zhou, Y Timm, K Shanmuganathan, M Pulous, FE Schloss, MJ Foy, BH Capen, D Vinegoni, C Wojtkiewicz, GR Iwamoto, Y Grune, T Brown, D Higgins, J Ferreira, VM Herring, N Channon, KM Neubauer, S Sosnovik, DE Milan, DJ Swirski, FK King, KR Aguirre, AD Ellinor, PT Nahrendorf, M |
| author_sort | Grune, J |
| collection | OXFORD |
| description | 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 <i>Ccr2<sup>−/−</sup></i> mice or all macrophage subsets with Csf1 receptor inhibition increased both ventricular tachycardia and fibrillation. Higher arrhythmia burden and mortality in <i>Cd36<sup>−/−</sup></i> and <i>Mertk<sup>−/−</sup></i> 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. |
| first_indexed | 2024-03-07T08:01:10Z |
| format | Journal article |
| id | oxford-uuid:db5cdfda-51ed-485a-873f-1298a0186205 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T08:01:10Z |
| publishDate | 2022 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:db5cdfda-51ed-485a-873f-1298a01862052023-09-20T17:00:18ZNeutrophils incite and macrophages avert electrical storm after myocardial infarctionJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:db5cdfda-51ed-485a-873f-1298a0186205Monocytes and macrophagesCardiovascular modelsCardiovascular diseasesEnglishSymplectic ElementsSpringer Nature2022Grune, JLewis, AJMYamazoe, MHulsmans, MRohde, DXiao, LZhang, SOtt, CCalcagno, DMZhou, YTimm, KShanmuganathan, MPulous, FESchloss, MJFoy, BHCapen, DVinegoni, CWojtkiewicz, GRIwamoto, YGrune, TBrown, DHiggins, JFerreira, VMHerring, NChannon, KMNeubauer, SSosnovik, DEMilan, DJSwirski, FKKing, KRAguirre, ADEllinor, PTNahrendorf, MOxford Acute Myocardial Infarction (OxAMI) StudySudden 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 <i>Ccr2<sup>−/−</sup></i> mice or all macrophage subsets with Csf1 receptor inhibition increased both ventricular tachycardia and fibrillation. Higher arrhythmia burden and mortality in <i>Cd36<sup>−/−</sup></i> and <i>Mertk<sup>−/−</sup></i> 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. |
| spellingShingle | Monocytes and macrophages Cardiovascular models Cardiovascular diseases Grune, J Lewis, AJM Yamazoe, M Hulsmans, M Rohde, D Xiao, L Zhang, S Ott, C Calcagno, DM Zhou, Y Timm, K Shanmuganathan, M Pulous, FE Schloss, MJ Foy, BH Capen, D Vinegoni, C Wojtkiewicz, GR Iwamoto, Y Grune, T Brown, D Higgins, J Ferreira, VM Herring, N Channon, KM Neubauer, S Sosnovik, DE Milan, DJ Swirski, FK King, KR Aguirre, AD Ellinor, PT Nahrendorf, M Neutrophils incite and macrophages avert electrical storm after myocardial infarction |
| title | Neutrophils incite and macrophages avert electrical storm after myocardial infarction |
| title_full | Neutrophils incite and macrophages avert electrical storm after myocardial infarction |
| title_fullStr | Neutrophils incite and macrophages avert electrical storm after myocardial infarction |
| title_full_unstemmed | Neutrophils incite and macrophages avert electrical storm after myocardial infarction |
| title_short | Neutrophils incite and macrophages avert electrical storm after myocardial infarction |
| title_sort | neutrophils incite and macrophages avert electrical storm after myocardial infarction |
| topic | Monocytes and macrophages Cardiovascular models Cardiovascular diseases |
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