Sleep is integral to cardiovascular health1,2.
A possible relationship with poor or inadequate sleep cycles and the effect of poor sleeping habits may contribute to acute myocardial infarction.
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 tumor 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 signaling 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 toward 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.
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