Hyperbaric oxygen therapy alleviates acute carbon monoxide poisoning-induced transition of cardiac fibroblast to myofibroblast and ameliorates cardiac fibrosis via the NRF2/ROS/TGFβ1/Smad pathway.

Abstract

BACKGROUND: Acute carbon monoxide poisoning (ACOP) is one of the leading causes of poisoning-related deaths worldwide, inducing severe complications such as myocardial fibrosis and cardiac dysfunction. Hyperbaric oxygen (HBO) therapy is an effective clinical treatment for carbon monoxide (CO) poisoning, but its underlying mechanisms require further investigation. METHODS: An ACOP mouse model was established and treated with HBO. Carboxyhemoglobin (COHb) levels were measured, and myocardial histopathological changes and collagen deposition were determined via hematoxylin-eosin staining, Masson's trichrome staining, and immunohistochemical staining. An ACOP cell model was constructed in the human cardiac fibroblast line HCF. Cell proliferation and migration were tested in CCK-8 and Transwell assays. The DHE fluorescent probe was applied in the determination of intracellular reactive oxygen species (ROS) levels. Alpha-Smooth Muscle Actin (α-SMA) expression was examined by immunofluorescence. Finally, qRT-PCR and Western blot were used to measure the expression of fibrosis markers and proteins related to the Nuclear Factor Erythroid 2-Related Factor 2 (NRF2)/Transforming Growth Factor Beta 1 (TGF-β1)/Mothers Against Decapentaplegic Homolog (Smad) pathway. RESULTS: HBO therapy significantly reduced COHb levels, improved myocardial histopathological changes and collagen deposition, repressed cell proliferation and migration, and alleviated oxidative stress. Mechanistically, HBO therapy activated the NRF2 signaling pathway, reduced ROS levels, and suppressed the TGF-β1/Smad signaling pathway, thus mitigating the transition of cardiac fibroblasts to myofibroblasts. CONCLUSION: HBO therapy effectively represses ACOP-induced cardiac fibroblast-to-myofibroblast transition and ameliorates cardiac fibrosis by modulating the NRF2/ROS/TGF-β1/Smad signaling pathway.

Key Findings

• Hyperbaric oxygen (HBO) therapy significantly reduced carboxyhemoglobin (COHb) levels and improved myocardial histopathological changes and collagen deposition in an acute carbon monoxide poisoning (ACOP) mouse model.
• HBO therapy repressed cardiac fibroblast proliferation and migration and alleviated oxidative stress by reducing intracellular reactive oxygen species (ROS) levels.
• HBO activated the NRF2 signaling pathway and suppressed the TGF-β1/Smad signaling pathway, thereby mitigating the transition of cardiac fibroblasts to myofibroblasts and ameliorating cardiac fibrosis.

Clinical Significance

Citation

Wang Jianfei, Shi Binhao, Hao Yanchenget al.. Hyperbaric oxygen therapy alleviates acute carbon monoxide poisoning-induced transition of cardiac fibroblast to myofibroblast and ameliorates cardiac fibrosis via the NRF2/ROS/TGFβ1/Smad pathway. European journal of pharmacology. 2026-Jun-28.