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Sleep fragmentation exacerbates myocardial ischemia‒reperfusion injury by promoting copper overload in cardiomyocytes

Author

Listed:
  • Na Chen

    (Central South University)

  • Lizhe Guo

    (Central South University)

  • Lu Wang

    (Central South University)

  • Sisi Dai

    (Central South University)

  • Xiaocheng Zhu

    (Central South University)

  • E. Wang

    (Central South University
    National Clinical Research Center for Geriatric Disorders (Xiangya Hospital))

Abstract

Sleep disorders increase the risk and mortality of heart disease, but the brain-heart interaction has not yet been fully elucidated. Cuproptosis is a copper-dependent type of cell death activated by the excessive accumulation of intracellular copper. Here, we showed that 16 weeks of sleep fragmentation (SF) resulted in elevated copper levels in the male mouse heart and exacerbated myocardial ischemia–reperfusion injury with increased myocardial cuproptosis and apoptosis. Mechanistically, we found that SF promotes sympathetic overactivity, increases the germination of myocardial sympathetic nerve terminals, and increases the level of norepinephrine in cardiac tissue, thereby inhibits VPS35 expression and leads to impaired ATP7A related copper transport and copper overload in cardiomyocytes. Copper overload further leads to exacerbated cuproptosis and apoptosis, and these effects can be rescued by excision of the sympathetic nerve or administration of copper chelating agent. Our study elucidates one of the molecular mechanisms by which sleep disorders aggravate myocardial injury and suggests possible targets for intervention.

Suggested Citation

  • Na Chen & Lizhe Guo & Lu Wang & Sisi Dai & Xiaocheng Zhu & E. Wang, 2024. "Sleep fragmentation exacerbates myocardial ischemia‒reperfusion injury by promoting copper overload in cardiomyocytes," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48227-y
    DOI: 10.1038/s41467-024-48227-y
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    References listed on IDEAS

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    1. Cameron S. McAlpine & Máté G. Kiss & Sara Rattik & Shun He & Anne Vassalli & Colin Valet & Atsushi Anzai & Christopher T. Chan & John E. Mindur & Florian Kahles & Wolfram C. Poller & Vanessa Froderman, 2019. "Sleep modulates haematopoiesis and protects against atherosclerosis," Nature, Nature, vol. 566(7744), pages 383-387, February.
    2. Lijun Wang & Jiaqi Wang & Pujiao Yu & Jingyi Feng & Gui-e Xu & Xuan Zhao & Tianhui Wang & H. Immo Lehmann & Guoping Li & Joost P. G. Sluijter & Junjie Xiao, 2022. "METTL14 is required for exercise-induced cardiac hypertrophy and protects against myocardial ischemia-reperfusion injury," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
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