{
  "abstract": "BACKGROUND: Pathological cardiac hypertrophy is a key precursor to heart failure. PAI-1 (plasminogen activator inhibitor-1) is a recognized profibrotic mediator, yet its role in the heart remains paradoxical and incompletely understood. METHODS: ) mice underwent sham or transverse aortic constriction surgery, followed by assessment of cardiac morphology, molecular markers, and function. In H9C2 cardiomyocytes, PAI-1 was silenced or overexpressed before angiotensin II stimulation, with or without targeted signaling inhibitors, followed by coimmunoprecipitation, Western blotting, and immunofluorescence. RESULTS: Pressure overload increased plasma and myocardial PAI-1 levels. PAI-1 deficiency exacerbated transverse aortic constriction-induced cardiac dysfunction, hypertrophy, and fibrosis, accompanied by JAK2/STAT3 (Janus kinase 2/signal transducer and activator of transcription 3) activation and collagen overexpression, whereas cardiac-specific overexpression attenuated these maladaptive changes. Moreover, STAT3 inhibition reversed the adverse cardiac remodeling associated with PAI-1 deletion. In vitro, PAI-1 knockdown potentiated angiotensin II-induced cardiomyocyte hypertrophy, an effect that was rescued by PAI-1 overexpression. Mechanistically, PAI-1 associated with JAK2 and STAT3, with reduced phosphorylation of both proteins and impaired STAT3 nuclear translocation. Critically, pharmacological inhibition of STAT3 abolished the harmful effects of PAI-1 silencing. CONCLUSIONS: PAI-1 acts as an endogenous cardioprotective checkpoint by negatively regulating JAK2/STAT3 signaling. These findings suggest a noncanonical cardiomyocyte-associated function of PAI-1 beyond its classical fibrinolytic role and identify the PAI-1-JAK2/STAT3 axis as a potential therapeutic target for heart failure with hypertrophy.",
  "abstract_shown": true,
  "affiliations": [
    "The First Hospital of Jilin University",
    "The Affiliated Hospital of Southwest Medical University",
    "Yanbian University",
    "Nagoya University Graduate School of Medicine",
    "Yanbian University Hospital"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Chaoqun Huang"
    },
    {
      "affs": [
        0
      ],
      "name": "Shangzhi Shu",
      "orcid": "0000-0001-7462-5124"
    },
    {
      "affs": [
        2
      ],
      "name": "Xueling Yue",
      "orcid": "0000-0002-8589-5397"
    },
    {
      "affs": [
        2
      ],
      "name": "Jinshun Piao",
      "orcid": "0009-0000-2234-4371"
    },
    {
      "affs": [
        3
      ],
      "name": "Megumi Narisawa",
      "orcid": "0009-0000-6581-4708"
    },
    {
      "affs": [
        2
      ],
      "name": "Chongning Zhong",
      "orcid": "0009-0002-1112-1214"
    },
    {
      "affs": [
        2
      ],
      "name": "Longguo Zhao"
    },
    {
      "affs": [
        2
      ],
      "name": "Na Wang"
    },
    {
      "affs": [
        2
      ],
      "name": "Huayang Zhang"
    },
    {
      "affs": [
        2
      ],
      "name": "Yongyan Chen",
      "orcid": "0009-0005-2323-6694"
    },
    {
      "affs": [
        2
      ],
      "name": "Meiping Zhang",
      "orcid": "0009-0008-4517-7420"
    },
    {
      "affs": [
        2,
        4
      ],
      "name": "Xian Wu Cheng",
      "orcid": "0000-0002-9758-0632"
    },
    {
      "affs": [
        0
      ],
      "name": "Shuyan Li"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fppe6a7146nxc.bib",
  "cited_by": 0,
  "doi": "10.1161/jaha.126.052213",
  "fulltext_url": null,
  "id": "fppe6a7146nxc",
  "issns": [
    "2047-9980"
  ],
  "landing_url": "https://www.ahajournals.org/doi/10.1161/JAHA.126.052213",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2705|Cardiac Fibrosis and Remodeling"
    ]
  ],
  "openalex": "W7223395971",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-23",
  "publisher": "Ovid Technologies (Wolters Kluwer Health)",
  "ris": "https://research.draconitic.com/paper/fppe6a7146nxc.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:28Z",
      "native_id": "10.1161/jaha.126.052213",
      "source": "crossref",
      "url": "https://www.ahajournals.org/doi/10.1161/JAHA.126.052213"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2705|Cardiac Fibrosis and Remodeling",
      "subfield": "cardiovascular"
    }
  ],
  "title": "Plasminogen Activator Inhibitor‐1 Deficiency Exacerbates Pressure Overload‐Induced Cardiac Hypertrophy in Mice",
  "title_text": "Plasminogen Activator Inhibitor‐1 Deficiency Exacerbates Pressure Overload‐Induced Cardiac Hypertrophy in Mice",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:28Z",
  "url": "https://research.draconitic.com/paper/fppe6a7146nxc",
  "venue": "Journal of the American Heart Association",
  "versions": []
}