{
  "abstract": "Excessive free radical production and dysregulated immune responses contribute to myocardial ischemia-reperfusion (IR) injury. However, the mechanisms by which macrophages regulate reactive oxygen species (ROS) homeostasis and orchestrate immune responses during IR injury remain elusive. Here, we show that glutamate dehydrogenase 1 (GLUD1) expression is induced in monocytes from patients with acute myocardial infarction after interventional therapy and in cardiac-recruited macrophages from mice subjected to IR injury. GLUD1-deficient macrophages exacerbate IR injury by increasing mitochondrial ROS accumulation and amplifying pro-inflammatory responses. Mechanistically, GLUD1 deficiency leads to mitochondrial ROS accumulation due to reduced NADPH/NADP⁺ and GSH/GSSG ratios during IR injury. Elevated mitochondrial ROS inhibits PHD2 activity, stabilizing HIF-1α and enhancing NF-κB signaling, promoting the release of pro-inflammatory factors and exacerbating myocardial damage. Systemic activation of GLUD1 or adoptive transfer of monocytes pre-treated with a GLUD1 activator preserved cardiac function and mitigated IR injury. These findings highlight macrophage GLUD1 as a critical regulator of redox balance and immune homeostasis, presenting a promising therapeutic target for alleviating IR injury and preserving cardiac function.",
  "abstract_shown": true,
  "affiliations": [
    "Zhejiang Key Laboratory of Cardiovascular Intervention and Precision Medicine, Engineering Research Center For Cardiovascular Innovative Devices of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.",
    "School of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, China.",
    "Zhejiang Key Laboratory of Cardiovascular Intervention and Precision Medicine of Sir Run Run Shaw Hospital, Zhejiang University-Lishui Joint Innovation Center For Life and Health, Zhejiang University, Hangzhou, China.",
    "College of Life Sciences-iCell Biotechnology Regenerative Biomedicine Laboratory, College of Life Sciences, Zhejiang University, Hangzhou, China.",
    "Laboratory of Tumor Inflammation and Angiogenesis, Center For Cancer Biology, VIB, Leuven, Belgium.",
    "Laboratory of Tumor Inflammation and Angiogenesis, Center For Cancer Biology, Department of Oncology, KU Leuven, Leuven, Belgium."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 17,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Tingting Jin"
    },
    {
      "affs": [
        0
      ],
      "name": "Chaojie Lai"
    },
    {
      "affs": [
        0
      ],
      "name": "Qingyan Zhou"
    },
    {
      "affs": [
        0
      ],
      "name": "Ruilin Wang"
    },
    {
      "affs": [
        1
      ],
      "name": "Yiping Tong"
    },
    {
      "affs": [
        0
      ],
      "name": "Wentao Chen",
      "orcid": "0000-0002-1580-7769"
    },
    {
      "affs": [
        0
      ],
      "name": "Nikola Rabrenovic"
    },
    {
      "affs": [
        0
      ],
      "name": "Tingyu Zhang",
      "orcid": "0009-0000-3368-008X"
    },
    {
      "affs": [
        1
      ],
      "name": "Xinrong Ren"
    },
    {
      "affs": [
        0
      ],
      "name": "Chengchen Huang"
    },
    {
      "affs": [
        0
      ],
      "name": "Jiawen Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Ran Li"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Luyang Yu",
      "orcid": "0000-0002-1301-6285"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Massimiliano Mazzone",
      "orcid": "0000-0001-8824-4015"
    },
    {
      "affs": [
        0
      ],
      "name": "Wenbin Zhang",
      "orcid": "0000-0003-4746-9570"
    },
    {
      "affs": [
        0
      ],
      "name": "Guosheng Fu",
      "orcid": "0000-0001-7027-0717"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Min Shang",
      "orcid": "0000-0003-4511-4290"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fnpjjc9gg1yhc.bib",
  "cited_by": 0,
  "doi": "10.1002/advs.78416",
  "fulltext_url": "https://europepmc.org/articles/PMC13717128",
  "id": "fnpjjc9gg1yhc",
  "issns": [
    "2198-3844"
  ],
  "landing_url": "https://europepmc.org/article/MED/42952152",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "2734|Cardiac Ischemia and Reperfusion"
    ]
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  "openalex": "W7224549983",
  "pdf_url": "https://europepmc.org/articles/PMC13717128?pdf=render",
  "pmcid": "PMC13717128",
  "pmid": "42952152",
  "published": "2026-10-28",
  "publisher": "Wiley",
  "ris": "https://research.draconitic.com/paper/fnpjjc9gg1yhc.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:20:33Z",
      "native_id": "MED:42952152",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42952152"
    },
    {
      "first_seen": "2026-11-02T12:21:30Z",
      "native_id": "PMC13717128",
      "source": "pmc",
      "url": "https://doi.org/10.1002/advs.78416"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2734|Cardiac Ischemia and Reperfusion",
      "subfield": "general"
    }
  ],
  "title": "Macrophage GLUD1 is Essential for Redox Balance and Immune Homeostasis in Cardiac Injury.",
  "title_text": "Macrophage GLUD1 is Essential for Redox Balance and Immune Homeostasis in Cardiac Injury.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-02T12:21:30Z",
  "url": "https://research.draconitic.com/paper/fnpjjc9gg1yhc",
  "venue": "Advanced science (Weinheim, Baden-Wurttemberg, Germany)",
  "versions": []
}