{
  "abstract": "Background: Doxorubicin (Dox) induces dose-dependent Dox–induced cardiotoxicity (DIC), but the chamber-specific molecular mechanisms remain unclear, as traditional analyses rely on whole-heart homogenates. Methods: We established rat acute single–dose and chronic cumulative–dose DIC models, and separated left atrium (L–atrium) and left ventricle (L–ventricle) tissues for subsequent detection. Liquid chromatography–tandem mass spectrometry (LC–MS/MS) was used to quantify regional Dox tissue and serum concentrations. Histological HE and Masson’s staining were used to evaluate myocardial structural injury and collagen deposition. Integrated chamber-specific bulk proteomics, phosphoproteomics, and untargeted metabolomics were applied to systematically compare molecular perturbations between the L-atrium and L-ventricle. Two–way factorial statistical decomposition coupled with functional enrichment analysis was subsequently performed to identify both shared and chamber-specific molecular signatures. Results: Histological staining confirmed pronounced obvious myocardial fibrosis in both the L–atrium and L–ventricle under chronic Dox exposure. LC–MS/MS revealed prominent L–atrium–predominant Dox accumulation in the acute model, while inter–chamber drug distribution differences vanished after long–term repeated administration. Proteomic and metabolomic responses exhibited high inter–chamber consistency (r = 0.864 and r = 0.911, respectively). In contrast, the phosphoproteome was the dominant regulatory layer driving chamber divergence. A total of 14 core phosphosites with significant tissue–drug interaction effects were identified as key molecular switches. Conclusions: Our findings reveal preferential atrial Dox accumulation and distinct atrial phosphorylation remodeling following Dox exposure. The identified differential phosphosites serve as promising candidate targets for chamber-specific cardioprotection against DIC, pending further functional validation.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China",
    "Institute of Cardio-Oncology, Fudan University (in preparation), Shanghai 200032, China",
    "State Key Laboratory of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China",
    "Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, China",
    "Department of Echocardiography, Zhongshan Hospital, Fudan University, Shanghai 200032, China",
    "Zhongshan Hospital and Institute of Biomedical Sciences, Fudan University, 180 Fenglin Road, Shanghai 200032, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Jian Zhang"
    },
    {
      "affs": [
        1,
        3,
        4
      ],
      "name": "Yue Sun"
    },
    {
      "affs": [
        1,
        3,
        4
      ],
      "name": "Xiaozhen He"
    },
    {
      "affs": [
        1,
        3,
        4
      ],
      "name": "Yerui Zhang"
    },
    {
      "affs": [
        1,
        3,
        5
      ],
      "name": "Shijun Wang"
    },
    {
      "affs": [
        1,
        3,
        4
      ],
      "name": "Leilei Cheng",
      "orcid": "0000-0003-0677-7892"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3ftrzc5dw84rp.bib",
  "cited_by": 0,
  "doi": "10.3390/metabo16100746",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13706825/?tool=EBI",
  "id": "3ftrzc5dw84rp",
  "issns": [
    "2218-1989"
  ],
  "landing_url": "https://www.mdpi.com/2218-1989/16/10/746",
  "language": "eng",
  "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",
      "2705|Chemotherapy-induced cardiotoxicity and mitigation"
    ]
  ],
  "openalex": "W7220455609",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13706825/pdf/?tool=EBI",
  "pmcid": "PMC13706825",
  "pmid": null,
  "published": "2026-10-01",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/3ftrzc5dw84rp.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:00Z",
      "native_id": "10.3390/metabo16100746",
      "source": "crossref",
      "url": "https://www.mdpi.com/2218-1989/16/10/746"
    },
    {
      "first_seen": "2026-10-30T12:21:45Z",
      "native_id": "PMC:PMC13706825",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13706825"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2705|Chemotherapy-induced cardiotoxicity and mitigation",
      "subfield": "cardiovascular"
    }
  ],
  "title": "Chamber–Specific Molecular Profiling of Doxorubicin-Induced Cardiotoxicity via Integrated Multi-Omics Analysis",
  "title_text": "Chamber–Specific Molecular Profiling of Doxorubicin-Induced Cardiotoxicity via Integrated Multi-Omics Analysis",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:45Z",
  "url": "https://research.draconitic.com/paper/3ftrzc5dw84rp",
  "venue": "Metabolites",
  "versions": []
}