{
  "abstract": "PurposeChronic intermittent hypoxia (CIH), a defining pathophysiological feature of obstructive sleep apnea (OSA), imposes recurrent hypoxia–reoxygenation stress on the vascular endothelium. The metabolic–redox mechanisms connecting CIH to endothelial ferroptosis remain incompletely defined. This study investigated the pentose phosphate pathway (PPP)/glucose-6-phosphate dehydrogenase (G6PD)/NADPH axis in CIH-induced endothelial ferroptosis and evaluated the protective effects of Liproxstatin-1 (Lip-1).MethodsRats and rat aortic endothelial cells (RAOECs) were exposed to CIH and treated with Lip-1 or vehicle. Endothelial injury, ferroptosis-associated changes, and PPP-related metabolism were assessed using histopathology, Western blotting, flow cytometry, biochemical assays, electron microscopy, and targeted metabolomics. G6PD knockdown was used to examine its contribution to Lip-1-mediated protection.ResultsIn rats, CIH caused aortic endothelial injury accompanied by reduced GPX4 and SLC7A11 expression and increased ACSL4 expression. In RAOECs, CIH induced ferroptosis-associated changes, including increased Fe²+, lipid peroxidation, and mitochondrial abnormalities. CIH was also associated with reduced PPP-related metabolites, G6PD protein expression, and the NADPH/NADP+ ratio. Lip-1 attenuated endothelial injury and ferroptotic responses while restoring PPP/G6PD/NADPH-associated metabolic and redox parameters. G6PD knockdown partially attenuated the protective response to Lip-1.ConclusionCIH-associated endothelial ferroptotic injury is closely linked to altered PPP/G6PD-dependent redox metabolism. Lip-1 protects the endothelium while restoring this metabolic–redox axis, with G6PD contributing to its antioxidant and anti-ferroptotic effects.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China",
    "Department of Respiratory and Critical Care Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China",
    "Respiratory Disease Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 27,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Wenqian Chen"
    },
    {
      "affs": [
        1
      ],
      "name": "Wenqian Chen"
    },
    {
      "affs": [
        2
      ],
      "name": "Wenqian Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Jia Chen"
    },
    {
      "affs": [
        1
      ],
      "name": "Jia Chen"
    },
    {
      "affs": [
        2
      ],
      "name": "Jia Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Hansheng Xie"
    },
    {
      "affs": [
        1
      ],
      "name": "Hansheng Xie"
    },
    {
      "affs": [
        2
      ],
      "name": "Hansheng Xie"
    },
    {
      "affs": [
        0
      ],
      "name": "Fan Wei"
    },
    {
      "affs": [
        1
      ],
      "name": "Fan Wei"
    },
    {
      "affs": [
        2
      ],
      "name": "Fan Wei"
    },
    {
      "affs": [
        0
      ],
      "name": "Shiyuan Huang"
    },
    {
      "affs": [
        1
      ],
      "name": "Shiyuan Huang"
    },
    {
      "affs": [
        2
      ],
      "name": "Shiyuan Huang"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaoyu Deng"
    },
    {
      "affs": [
        1
      ],
      "name": "Xiaoyu Deng"
    },
    {
      "affs": [
        2
      ],
      "name": "Xiaoyu Deng"
    },
    {
      "affs": [
        0
      ],
      "name": "Yaqi Liu"
    },
    {
      "affs": [
        1
      ],
      "name": "Yaqi Liu"
    },
    {
      "affs": [
        2
      ],
      "name": "Yaqi Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Qichang Lin"
    },
    {
      "affs": [
        1
      ],
      "name": "Qichang Lin"
    },
    {
      "affs": [
        2
      ],
      "name": "Qichang Lin"
    },
    {
      "affs": [
        0
      ],
      "name": "Ningfang Lian"
    },
    {
      "affs": [
        1
      ],
      "name": "Ningfang Lian"
    },
    {
      "affs": [
        2
      ],
      "name": "Ningfang Lian"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ask4wdcttn0qn.bib",
  "cited_by": 0,
  "doi": "10.3389/fphys.2026.1971105",
  "fulltext_url": "https://www.frontiersin.org/articles/10.3389/fphys.2026.1971105/full",
  "id": "ask4wdcttn0qn",
  "issns": [
    "1664-042X"
  ],
  "landing_url": "https://doi.org/10.3389/fphys.2026.1971105",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
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      "lcc",
      "QP1-981"
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  "pmcid": null,
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  "published": "2026-11-09",
  "publisher": "Frontiers Media S.A.",
  "ris": "https://research.draconitic.com/paper/ask4wdcttn0qn.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T14:21:33Z",
      "native_id": "09454b8a5b064f08b003085f62db3c6a",
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      "url": "https://doi.org/10.3389/fphys.2026.1971105"
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  "subjects": [
    {
      "field": "medicine",
      "origin": "lcc:QP1-981",
      "subfield": "physiology"
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  ],
  "title": "G6PD-mediated pentose phosphate pathway modulates ferroptosis in chronic intermittent hypoxia-induced vascular endothelial injury",
  "title_text": "G6PD-mediated pentose phosphate pathway modulates ferroptosis in chronic intermittent hypoxia-induced vascular endothelial injury",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T14:21:33Z",
  "url": "https://research.draconitic.com/paper/ask4wdcttn0qn",
  "venue": "Frontiers in Physiology",
  "versions": []
}