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

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  • Additional Information
    • Source:
      Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
    • Publication Information:
      Original Publication: [London] : Nature Pub. Group
    • Subject Terms:
      Myocytes, Cardiac*/metabolism ; Myocytes, Cardiac*/pathology ; Copper*/metabolism ; Myocardial Reperfusion Injury*/metabolism ; Myocardial Reperfusion Injury*/pathology ; Sleep Deprivation*/physiopathology ; Sleep Deprivation*/metabolism ; Sleep Deprivation*/complications ; Apoptosis* ; Mice, Inbred C57BL*; Animals ; Male ; Mice ; Copper-Transporting ATPases/metabolism ; Copper-Transporting ATPases/genetics ; Norepinephrine/metabolism ; Norepinephrine/pharmacology ; Myocardium/metabolism ; Myocardium/pathology ; Sympathetic Nervous System/metabolism ; Disease Models, Animal
    • 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.
      (© 2024. The Author(s).)
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    • Grant Information:
      82170291 National Natural Science Foundation of China (National Science Foundation of China); 81800058 National Natural Science Foundation of China (National Science Foundation of China)
    • Accession Number:
      789U1901C5 (Copper)
      EC 7.2.2.8 (Copper-Transporting ATPases)
      X4W3ENH1CV (Norepinephrine)
      0 (Atp7a protein, mouse)
    • Publication Date:
      Date Created: 20240507 Date Completed: 20240507 Latest Revision: 20240510
    • Publication Date:
      20240510
    • Accession Number:
      PMC11076509
    • Accession Number:
      10.1038/s41467-024-48227-y
    • Accession Number:
      38714741