Sleep modulates haematopoiesis and protects against atherosclerosis
Open accessAbstract
Sleep is integral to life 1. Although insufficient or disrupted sleep increases the risk of multiple pathological conditions, including cardiovascular disease 2, 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-6C high 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.
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Biological mechanisms include neuroinflammation, atherosclerosis, alpha-synucleinopathies, and impaired amyloidβ clearance.
“Biological mechanisms include neuroinflammation,(312) atherosclerosis,(313) alpha-synucleinopathies (dementia with Lewy bodies and Parkinson disease dementia),(314) and impaired amyloidβ clearance. (315)”
From Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission (2024) · cites this paper as [313]
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- Authors
- McAlpine, C. S., Kiss, M. G., Rattik, S., He, S., Vassalli, A., Valet, C., Anzai, A., Chan, C. T., Mindur, J. E., Kahles, F., Poller, W. C., Frodermann, V., Fenn, A. M., Gregory, A. F., Halle, L., Iwamoto, Y., Hoyer, F. F., Binder, C. J., Libby, P., Tafti, M., Scammell, T. E., Nahrendorf, M., & Swirski, F. K.
- Affiliations
- Harvard University (US)
- University of Lausanne (CH)
- Austrian Academy of Sciences (AT)
- Brigham and Women's Hospital (US)
- Beth Israel Deaconess Medical Center (US)
- ORCID
- McAlpine, Cameron S.
- Kiss, Máté G.
- Rattik, Sara
- He, Shun
- Vassalli, Anne
- Anzai, Atsushi
- Chan, Christopher T.
- Mindur, John E.
- Kahles, Florian
- Poller, Wolfram C.
- Frodermann, Vanessa
- Halle, Lennard
- Iwamoto, Yoshiko
- Hoyer, Friedrich F.
- Binder, Christoph J.
- Libby, Peter
- Tafti, Mehdi
- Scammell, Thomas E.
- Nahrendorf, Matthias
- Venue
- Nature
- Published
- 2019-02-13
- Volume
- 566
- Issue
- 7744
- Pages
- 383-387
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC6442744
- OpenAlex
- W2912600324
- Cited by
- 447
- References
- 44
- Citations by year
- 2026: 43 · 2025: 72 · 2024: 58 · 2023: 58 · 2022: 55 · 2021: 58 · 2020: 59 · 2019: 43
- FWCI
- 31.03
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- SERVAL (Université de Lausanne) (acceptedVersion, other-oa)
- IRIS (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Science Foundation
- American Heart Association
- Deutsche Forschungsgemeinschaft (331536185, 398190272)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (125323)
- Austrian Science Fund
- Vetenskapsrådet
- National Institutes of Health
- Canadian Institutes of Health Research
- National Heart, Lung, and Blood Institute (R35HL135752, R01HL128264, R35HL139598, R01HL095612, P01HL131478)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Physiology › Obstructive Sleep Apnea Research
- Keywords
- sleep fragmentation, hematopoiesis, atherosclerosis, orexin, CSF-1, myelopoiesis, monocytes, neuroimmune axis, bone marrow, ApoE-deficient mice, cardiovascular disease, hypocretin receptor
- MeSH terms
- Orexins, Animals, Antigens, Ly, Bone Marrow Cells, Female, Hematopoiesis, Hypothalamic Area, Lateral, Male, Monocytes, Neutrophils, Sleep, Sleep Deprivation, Macrophage Colony-Stimulating Factor, Myelopoiesis, Atherosclerosis, Mice, Orexin Receptors
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