{
  "abstract": "Aortic dissection (AD) is a catastrophic cardiovascular emergency triggered by severe pathological stress. While continuous stress drives vascular smooth muscle cell (VSMC) apoptosis via mitochondrial dysfunction, the precise upstream orchestrators linking these stress signals to the mitochondrial apoptotic cascade remain elusive. By integrating clinical observations and single-cell RNA sequencing, we found that Nuclear Protein 1 (Nupr1), a critical stress-responsive factor, is significantly upregulated in aortas from AD patients and murine models, with enrichment in VSMCs. Remarkably, VSMC-specific Nupr1 deficiency significantly ameliorated AD progression in vivo. Mechanistically, Nupr1 undergoes massive mitochondrial accumulation in Ang II-induced apoptotic VSMCs. Rather than operating as a conventional transcriptional regulator, mitochondrially enriched Nupr1 functions as a pathological spatial switch. It sequesters p53 within mitochondria, driving transcription-independent apoptosis while simultaneously blunting the protective Gadd45b-mediated survival program. Furthermore, in vivo Gadd45b overexpression was sufficient to rescue mitochondrial dysfunction and ameliorate vascular collapse. Taken together, our findings conceptualize the Nupr1-p53-Gadd45b axis as an important determinant of VSMC fate and provide a novel and promising therapeutic strategy for preventing AD progression.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Cardiovascular Surgery, Fujian Medical University Union Hospital, Fuzhou, China.",
    "Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fujian Province University, Fuzhou, China.",
    "Engineering Research Center of Tissue and Organ Regeneration, Fujian Province University, Fuzhou, China.",
    "Department of Anesthesiology, Union Hospital, Fujian Medical University, Fuzhou, China.",
    "The School of Pharmacy, Fujian Medical University, Fuzhou, China.",
    "Fujian Center for Safety Evaluation of New Drug, Fujian Medical University, Fuzhou, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Xi Yang",
      "orcid": "0000-0002-5814-8708"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Ke-Yuan Chen"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Yue Tian",
      "orcid": "0000-0002-9139-6658"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Zong-Sheng Jiang"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Jian Lei",
      "orcid": "0000-0002-5214-4730"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Xing-Hui Zhuang",
      "orcid": "0000-0003-4342-5597"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Jiang-Bin Wu",
      "orcid": "0009-0003-3177-2265"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Le-Le Tang"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Hao-Yu Li"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Xiao-Hui Chen"
    },
    {
      "affs": [
        3
      ],
      "name": "Yue Wang"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Yu-Mei Li",
      "orcid": "0000-0002-6158-7488"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Zhi-Huang Qiu",
      "orcid": "0000-0002-5917-8968"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Zi-Wen Cai"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Liang-Wan Chen",
      "orcid": "0000-0002-4211-3842"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e5tr1ww8twyfd.bib",
  "cited_by": 0,
  "doi": "10.1002/advs.78143",
  "fulltext_url": "https://europepmc.org/articles/PMC13672869",
  "id": "e5tr1ww8twyfd",
  "issns": [
    "2198-3844"
  ],
  "landing_url": "https://europepmc.org/article/MED/42881547",
  "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": [
    [
      "openalex",
      "2740|Aortic Disease and Treatment Approaches"
    ]
  ],
  "openalex": "W7222669906",
  "pdf_url": "https://europepmc.org/articles/PMC13672869?pdf=render",
  "pmcid": "PMC13672869",
  "pmid": "42881547",
  "published": "2026-10-15",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/e5tr1ww8twyfd.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:46Z",
      "native_id": "MED:42881547",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42881547"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2740|Aortic Disease and Treatment Approaches",
      "subfield": "general"
    }
  ],
  "title": "Targeting Nupr1-Mediated p53 Mitochondrial Sequestration Alleviates Aortic Dissection by Restoring the Gadd45b-Dependent Survival Program.",
  "title_text": "Targeting Nupr1-Mediated p53 Mitochondrial Sequestration Alleviates Aortic Dissection by Restoring the Gadd45b-Dependent Survival Program.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:46Z",
  "url": "https://research.draconitic.com/paper/e5tr1ww8twyfd",
  "venue": "Advanced science (Weinheim, Baden-Wurttemberg, Germany)",
  "versions": []
}