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Heart failure

Heart disease causes sleep disturbances via neuroimmune mechanisms

Nature Reviews Cardiology volume 20, page 649 (2023)Cite this article

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A study reveals that the disrupted sleep patterns that are frequently observed in patients with cardiac disease are driven by immune-mediated sympathetic denervation and dysfunction of the pineal gland, which leads to a decrease in the circulating levels of melatonin and subsequent sleep disruption. These findings, published in Science, highlight a mechanistic link between cardiac disease and sleep–wake cycle disruptions and a novel target for therapeutic intervention in these patients, as well as a previously unknown connection between the immune and sympathetic nervous system.

“We found that cardiac disease causes severe and irreversible damage to a specific subset of sympathetic neurons that control the diurnal rhythmicity of pineal release of melatonin,” says Ziegler. Immunostaining of sympathetic axons of pineal gland samples from mouse models of cardiac disease and autopsy specimens from patients with heart disease revealed substantial denervation compared with controls. The researchers were able to trace this defect in axonal density back to the SCG and found that cardiac disease causes fibrotic scarring and hypertrophy of the SCG, as well as infiltration of macrophages into the SCG in both mice and humans. In a mouse model of heart disease, depletion of macrophages in the SCG or inhibition of their activation prevented disease-associated denervation of the pineal gland and restored the normal physiological secretion of melatonin.

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References

Original article

  • Ziegler, K. A. et al. Immune-mediated denervation of the pineal gland underlies sleep disturbance in cardiac disease. Science 381, 285–290 (2023)

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Related article

  • Carnevale, D. Neuroimmune axis of cardiovascular control: mechanisms and therapeutic implications. Nat. Rev. Cardiol. 19, 379–394 (2022)

    Article  PubMed  Google Scholar 

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  1. Nature Reviews Cardiology http://www.nature.com/nrcardio/

    Irene Fernández-Ruiz

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  1. Irene Fernández-Ruiz
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Correspondence to Irene Fernández-Ruiz.

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Fernández-Ruiz, I. Heart disease causes sleep disturbances via neuroimmune mechanisms. Nat Rev Cardiol 20, 649 (2023). https://doi.org/10.1038/s41569-023-00921-y

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  • DOI: https://doi.org/10.1038/s41569-023-00921-y

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