{
  "abstract": "Background: Doxorubicin cardiotoxicity is a major clinical concern, but the role of PP2Ac α in this process remains unknown. This study investigated its involvement and underlying mechanisms.\n\nMethods: A mouse model of doxorubicin-induced myocardial injury was established. Cardiac function, cardiac morphology, cardiomyocyte size, myocardial fibrosis, and apoptosis were assessed by echocardiography, H&E staining, Masson's trichrome staining, immunofluorescence, TUNEL staining, qRT-PCR, and Western blotting. Cardiac-specific Ppp2ca conditional knockout mice ( Ppp2ca cKO ) were used to evaluate the effect of Ppp2ca deletion on doxorubicin cardiotoxicity. In vitro , cultured cardiomyocytes were treated with varying concentrations of doxorubicin, and PP2Ac α expression was silenced using Ppp2ca -siRNA to assess cell viability and apoptosis-related protein expression.\n\nResults: Doxorubicin treatment significantly reduced left ventricular ejection fraction (LVEF) and fractional shortening (LVFS), accompanied by increased left ventricular internal diameter at systole, reduced wall thickness, decreased heart weight-to-tibia length ratio, and reduced cardiomyocyte cross-sectional area, indicating impaired systolic function and myocardial atrophy; Doxorubicin also upregulated Ppp2ca mRNA and PP2Ac α protein expression in myocardial tissues and cardiomyocytes, while decreasing the anti-apoptotic protein Bcl-2 and increasing the pro-apoptotic proteins Bax and cleaved Caspase-3. Compared with Ppp2ca flox/flox mice, Ppp2ca cKO mice showed markedly attenuated cardiac dysfunction, cardiac atrophy, and cardiomyocyte size reduction after doxorubicin treatment. Masson's staining and Col1a1 /Col3a1 mRNA analysis further showed reduced myocardial collagen deposition. Moreover, the increase in TUNEL-positive cells and the abnormal expression of apoptosis-related proteins were markedly attenuated by Ppp2ca deletion. In vitro siRNA experiments confirmed that Ppp2ca knockdown improved cardiomyocyte viability and mitigated changes in apoptosis-related proteins after doxorubicin treatment.\n\nConclusion: Doxorubicin induces PP2Ac α upregulation in myocardial tissues and cardiomyocytes, whereas Ppp2ca deletion or knockdown effectively alleviates doxorubicin-induced cardiac dysfunction, myocardial fibrosis, and cardiomyocyte apoptosis. PP2Ac α acts as a key pro-injury factor in doxorubicin cardiotoxicity, and targeting Ppp2ca may represent a potential strategy for preventing anthracycline-induced cardiotoxicity.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Cardiology, The Second Nanning People’s Hospital",
    "Department of Cardiology, The Affiliated Jiangning Hospital of Nanjing Medical University"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Wei Huang"
    },
    {
      "affs": [
        1
      ],
      "name": "Xingyu Jiang"
    },
    {
      "affs": [
        1
      ],
      "name": "Wenjing Xu"
    },
    {
      "affs": [
        1
      ],
      "name": "Hao Zhang"
    },
    {
      "affs": [
        1
      ],
      "name": "Youpeng Geng"
    },
    {
      "affs": [
        1
      ],
      "name": "Lai Zhang"
    },
    {
      "affs": [
        1
      ],
      "name": "Chao Fang"
    },
    {
      "affs": [
        1
      ],
      "name": "Qin Tao"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/37exhht8kf86h.bib",
  "cited_by": 0,
  "doi": "10.3389/fcvm.2026.1994338",
  "fulltext_url": null,
  "id": "37exhht8kf86h",
  "issns": [
    "2297-055X"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fcvm.2026.1994338/full",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-04",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/37exhht8kf86h.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T12:21:45Z",
      "native_id": "10.3389/fcvm.2026.1994338",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fcvm.2026.1994338/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "issn:2297-055X",
      "subfield": "cardiovascular"
    }
  ],
  "title": "PP2Acα deficiency attenuates doxorubicin-induced cardiac injury by suppressing cardiomyocyte apoptosis",
  "title_text": "PP2Acα deficiency attenuates doxorubicin-induced cardiac injury by suppressing cardiomyocyte apoptosis",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T00:21:26Z",
  "url": "https://research.draconitic.com/paper/37exhht8kf86h",
  "venue": "Frontiers in Cardiovascular Medicine",
  "versions": []
}