Neuromodulation and Copper Chelation Reverse Sleep Fragmentation-Aggravated Myocardial Ischemia-Reperfusion Injury by...

Area of Science:

• Cardiovascular Research
• Sleep Medicine
• Cellular Biology

Background:

• Myocardial ischemia-reperfusion injury (MI/RI) is a significant clinical concern.
• Sleep disorders are increasingly recognized as risk factors for cardiovascular diseases.
• The precise mechanisms linking sleep disturbances to cardiac microvascular injury remain unclear.

Purpose of the Study:

• To investigate the impact of chronic sleep fragmentation (SF) on cardiac microvascular injury in a mouse model of MI/RI.
• To elucidate the underlying molecular mechanisms connecting SF to exacerbated cardiac damage.
• To identify potential therapeutic targets for mitigating SF-induced cardiovascular complications.

Main Methods:

• Mice were subjected to a 16-week sleep fragmentation protocol.
• An MI/RI model was induced to assess cardiac microvascular damage.
• Proteomic analyses were employed to explore underlying mechanisms, including sympathetic hyperactivity, neutrophil extracellular traps (NETs), and copper metabolism.

Main Results:

• Sixteen weeks of SF significantly intensified cardiac microvascular damage in MI/RI mice.
• SF induced sympathetic hyperactivity, elevated epinephrine, and promoted NET formation.
• NETs led to copper accumulation in cardiac microvascular endothelial cells (CMECs), oxidative stress, and cuproptosis, which were reversible by specific interventions.

Conclusions:

• Sleep fragmentation exacerbates MI/RI by promoting copper overload in CMECs via NET formation and impaired copper transport.
• Sympathetic hyperactivity plays a crucial role in mediating SF-induced cardiac microvascular injury.
• Targeting NETs, copper metabolism, or sympathetic overactivity presents potential therapeutic strategies for sleep-related cardiac complications.