Myocardial infarction augments sleep to limit cardiac inflammation and damage

• 成果类型: Article
• 署名作者: Huynh, Pacific; Hoffmann, Jan D.; Gerhardt, Teresa; Kiss, Mate G.; Zuraikat, Faris M.; Cohen, Oren; Wolfram, Christopher; Yates, Abi G.; Leunig, Alexander; Heiser, Merlin; Gaebel, Lena; Gianeselli, Matteo; Goswami, Sukanya; Khamhoung, Annie; Downey, Jeffrey; Yoon, Seonghun; Chen, Zhihong; Roudko, Vladimir; Dawson, Travis; Ferreira da Silva, Joana; Ameral, Natalie J.; Morgenroth-Rebin, Jarod; D'Souza, Darwin; Koekkoek, Laura L.; Jacob, Walter; Munitz, Jazz; Lee, Donghoon; Fullard, John F.; van Leent, Mandy M. T.; Roussos, Panos; Kim-Schulze, Seunghee; Shah, Neomi; Kleinstiver, Benjamin P.; Swirski, Filip K.; Leistner, David; St-Onge, Marie-Pierre; McAlpine, Cameron S.
• 署名单位: Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; German Heart Center Berlin; Humboldt University of Berlin; Free University of Berlin; Charite Universitatsmedizin Berlin; Berlin Institute of Health; Columbia University; NewYork-Presbyterian Hospital; NewYork-Presbyterian Hospital; Columbia University; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Goethe University Frankfurt; Goethe University Frankfurt Hospital
• 刊物名称: Nature
• ISSN/ISSBN: 0028-3771
• DOI: 10.1038/s41586-024-08100-w
• 发表日期: 2024-11-07
• 关键词: quality index; macrophages; validation; duration; brain

摘要

Sleep is integral to cardiovascular health1,2. 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 beta 2-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 beta 2-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. Studies in humans and mice show that myocardial infarction recruits monocytes to the brain's thalamus, promoting sleep, which in turn restricts cardiac inflammation and sympathetic signalling and assists healing.