Neutrophils incite and macrophages avert electrical storm after myocardial infarction

Nature Cardiovascular Research

  1. Nat. Card. Res.
    Neutrophils incite and macrophages avert electrical storm after myocardial infarction
    Grune, J., Lewis, A.J.M., Yamazoe, M., Hulsmans, M., Rohde, D., Xiao, L., Zhang, S., Ott, C., Calcagno, D.M., Zhou, Y., Timm, K., Shanmuganathan, M., Pulous, F.E., Schloss, M.J., Foy, B.H., Capen, D., Vinegoni, C., Wojtkiewicz, G.R., Iwamoto, I., Grune, T., Brown, D., Higgins, J., Ferreira, V.M., Herring, N., Channon, K.M., Neubauer, S., Study, Oxford Acute Myocardial Infarction (OxAMI), Sosnovik, D.E., Milan, D.J., Swirski, F.K., King, K.R., Aguirre, A.D., Ellinor, P.T., and Nahrendorf#, M.
    Nature Cardiovascular Research 2022

Abstract

"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."

Full citation

For attribution in academic contexts, please cite this work as:
Grune, J., Lewis, A. J. M., Yamazoe, M., Hulsmans, M., Rohde, D., Xiao, L., Zhang, S., Ott, C., Calcagno, D. M., Zhou, Y., Timm, K., Shanmuganathan, M., Pulous, F. E., Schloss, M. J., Foy, B. H., Capen, D., Vinegoni, C., Wojtkiewicz, G. R., Iwamoto, I., … Nahrendorf#, M. (2022). Neutrophils incite and macrophages avert electrical storm after myocardial infarction. Nature Cardiovascular Research, 1(1), 649–664. https://doi.org/10.1038/s44161-022-00094-w




Grune, J., Lewis, A. J. M., Yamazoe, M., Hulsmans, M., Rohde, D., Xiao, L., Zhang, S., Ott, C., Calcagno, D. M., Zhou, Y., Timm, K., Shanmuganathan, M., Pulous, F. E., Schloss, M. J., Foy, B. H., Capen, D., Vinegoni, C., Wojtkiewicz, G. R., Iwamoto, I., … Nahrendorf#, M. (2022). Neutrophils incite and macrophages avert electrical storm after myocardial infarction. Nature Cardiovascular Research, 1(1), 649–664. https://doi.org/10.1038/s44161-022-00094-w