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

Na Chen, Lizhe Guo, Lu Wang, Sisi Dai, Xiaocheng Zhu and E. Wang ()
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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

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-48227-y

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