美国纽约西奈山伊坎医学院Cameron S McAlpine研究团队报道，心肌梗塞增加睡眠以限制心脏炎症和损伤。相关论文于2024年10月30日发表于国际顶尖学术期刊《自然》杂志上。

据介绍，睡眠对心血管健康是不可或缺的。然而，连接心血管病理和睡眠的环路还没有完全被理解。目前尚不清楚心脏损伤是否会影响睡眠，以及睡眠介导的神经输出是否有助于心脏愈合和炎症。

研究人员报告了在人类和小鼠中，单核细胞在心肌梗塞后被积极招募到大脑以增加睡眠，这抑制了交感神经向心脏的流出，限制了炎症并促进了愈合。心肌梗塞后，小胶质细胞通过脉膜丛，迅速将循环单核细胞招募到大脑丘脑外侧后核（LPN），在那里它们被重新编程以产生肿瘤坏死因子（TNF）。

在丘脑LPN中，单核细胞TNF参与表达tnfrsf1a的谷氨酸能神经元，增加慢波睡眠压力和丰度。心肌梗塞后睡眠中断会使心功能恶化，降低心率可变性，诱发自发性室性心动过速。心肌梗塞后，控制丘脑LPN中的谷氨酸能TNF信号来干扰或缩短睡眠，会增加心脏交感神经输入，其通过巨噬细胞的β2-肾上腺素能受体发出信号，促进趋化信号，增加单核细胞内流。

急性冠状动脉综合征后数周睡眠不足，会增加继发性心血管事件的易感性，并降低心脏功能的恢复。与此同时，人类睡眠不足会使表达β2-肾上腺素能受体的单核细胞重编程为趋化表型，增强其迁移能力。总的来说，他们的数据揭示了心脏损伤后睡眠的心源性调节，这限制了心脏交感神经输入，控制了炎症和损伤。

附：英文原文

Title: Myocardial infarction augments sleep to limit cardiac inflammation and damage

Author: Huynh, Pacific, Hoffmann, Jan D., Gerhardt, Teresa, Kiss, Mt 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, DSouza, 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.

Issue&Volume: 2024-10-30

Abstract: 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 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.

DOI: 10.1038/s41586-024-08100-w

Source: https://www.nature.com/articles/s41586-024-08100-w