Short-term low oxygen at high altitude triggers inflammation in lung artery muscle cells by disrupting mitochondrial DNA through a daily rhythm protein

Mice exposed to a simulated altitude of 5500 m for 3 days exhibited significantly increased levels of inflammatory cytokines in pulmonary arteries.

• Hypoxia-induced inflammatory injury may contribute to acute mountain sickness.
• Mitochondrial DNA (mtDNA) release is associated with inflammation in various diseases.
• Activation of the NLRP3 inflammasome was observed in pulmonary artery smooth muscle cells (PASMCs) following hypoxic exposure.
• The core clock component BMAL1 regulates mtDNA leakage in PASMCs.
• Knocking out Bmal1 in smooth muscle significantly reduced pulmonary arterial inflammation under acute high-altitude hypoxia.
• BMAL1 may promote mtDNA leakage through the transcription of Voltage-dependent anion channel 1 (VDAC1), leading to vascular inflammation.

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