1. Myocardial infarction augments sleep to limit cardiac inflammation and damage.
- Author
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Huynh P, Hoffmann JD, Gerhardt T, Kiss MG, Zuraikat FM, Cohen O, Wolfram C, Yates AG, Leunig A, Heiser M, Gaebel L, Gianeselli M, Goswami S, Khamhoung A, Downey J, Yoon S, Chen Z, Roudko V, Dawson T, Ferreira da Silva J, Ameral NJ, Morgenroth-Rebin J, D'Souza D, Koekkoek LL, Jacob W, Munitz J, Lee D, Fullard JF, van Leent MMT, Roussos P, Kim-Schulze S, Shah N, Kleinstiver BP, Swirski FK, Leistner D, St-Onge MP, and McAlpine CS
- Subjects
- Animals, Female, Humans, Male, Mice, Chemotaxis, Leukocyte, Choroid Plexus metabolism, Glutamic Acid metabolism, Heart physiopathology, Heart Rate, Lateral Thalamic Nuclei metabolism, Macrophages cytology, Macrophages metabolism, Mice, Inbred C57BL, Microglia metabolism, Microglia pathology, Monocytes cytology, Monocytes metabolism, Neurons metabolism, Receptors, Adrenergic, beta-2 metabolism, Receptors, Tumor Necrosis Factor, Type I metabolism, Sleep, Slow-Wave physiology, Sympathetic Nervous System physiopathology, Tachycardia, Ventricular physiopathology, Tachycardia, Ventricular etiology, Tachycardia, Ventricular metabolism, Tumor Necrosis Factors metabolism, Inflammation pathology, Inflammation prevention & control, Myocardial Infarction physiopathology, Myocardial Infarction complications, Myocardial Infarction pathology, Myocardial Infarction metabolism, Myocardium pathology, Myocardium metabolism, Sleep physiology
- Abstract
Sleep is integral to cardiovascular health
1,2 . Yet, the circuits that connect cardiovascular pathology and sleep are incompletely understood. It remains unclear whether cardiac injury influences sleep and whether sleep-mediated neural outputs contribute to heart healing and inflammation. Here we report that in humans and mice, monocytes are actively recruited to the brain after myocardial infarction (MI) to augment sleep, which suppresses sympathetic outflow to the heart, limiting inflammation and promoting healing. After MI, microglia rapidly recruit circulating monocytes to the brain's thalamic lateral posterior nucleus (LPN) via the choroid plexus, where they are reprogrammed to generate tumour necrosis factor (TNF). In the thalamic LPN, monocytic TNF engages Tnfrsf1a-expressing glutamatergic neurons to increase slow wave sleep pressure and abundance. Disrupting sleep after MI worsens cardiac function, decreases heart rate variability and causes spontaneous ventricular tachycardia. After MI, disrupting or curtailing sleep by manipulating glutamatergic TNF signalling in the thalamic LPN increases cardiac sympathetic input which signals through the β2-adrenergic receptor of macrophages to promote a chemotactic signature that increases monocyte influx. Poor sleep in the weeks following acute coronary syndrome increases susceptibility to secondary cardiovascular events and reduces the heart's functional recovery. In parallel, insufficient sleep in humans reprogrammes β2-adrenergic receptor-expressing monocytes towards a chemotactic phenotype, enhancing their migratory capacity. Collectively, our data uncover cardiogenic regulation of sleep after heart injury, which restricts cardiac sympathetic input, limiting inflammation and damage., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2024
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