01 Apr Sleep modulates haematopoiesis and protects against atherosclerosis
Getting enough sleep is important to good health, and studies have shown that insufficient sleep increases the risk of serious problems, including cardiovascular disease. Recently published in the journal Nature, researchers have identified how a hormone in the brain controls processes in the bone marrow and protects against cardiovascular disease.
The study revealed that sleep-deprived mice had nearly two-fold increase in the production of stem cells in their bone marrow that give rise to white blood cells. The hormone hypocretin, produced in the hypothalamus and known to have a role in the regulation of sleep, was found to play a role in controlling white blood cell production. While normally produced at high levels when awake, hypocretin levels were significantly reduced in the sleep-deprived mice. This drop in hypocretin led to increased CSF-1 production by neutrophils, elevated monocyte production and accelerated atherosclerosis.
Sleep is integral to life. Although insufficient or disrupted sleep increases the risk of multiple pathological conditions, including cardiovascular disease, we know little about the cellular and molecular mechanisms by which sleep maintains cardiovascular health. Here we report that sleep regulates haematopoiesis and protects against atherosclerosis in mice. We show that mice subjected to sleep fragmentation produce more Ly-6Chigh monocytes, develop larger atherosclerotic lesions and produce less hypocretin—a stimulatory and wake-promoting neuropeptide—in the lateral hypothalamus. Hypocretin controls myelopoiesis by restricting the production of CSF1 by hypocretin-receptor-expressing pre-neutrophils in the bone marrow. Whereas hypocretin-null and haematopoietic hypocretin-receptor-null mice develop monocytosis and accelerated atherosclerosis, sleep-fragmented mice with either haematopoietic CSF1 deficiency or hypocretin supplementation have reduced numbers of circulating monocytes and smaller atherosclerotic lesions. Together, these results identify a neuro-immune axis that links sleep to haematopoiesis and atherosclerosis.
McAlpine CS, Kiss MG, Rattik S, He S, Vassalli A, Valet C, Anzai A, Chan CT, Mindur JE, Kahles F, Poller WC, Frodermann V, Fenn AM, Gregory AF, Halle L, Iwamoto Y, Hoyer FF, Binder CJ, Libby P, Tafti M, Scammell TE, Nahrendorf M, Swirski FK. Sleep modulates haematopoiesis and protects against atherosclerosis. Nature, 2019 DOI: 10.1038/s41586-019-0948-2