{
  "abstract": "Purpose: The molecular mechanisms linking vascular aging (VA) and heart failure (HF) remain elusive, hindering therapeutic strategies for their comorbidity. This study aimed to identify key biomarkers and pathways potentially involved in VA-HF synergy using integrative computational approaches. Methods: We analyzed the GSE57338 dataset (136 controls, 177 HF samples) to identify HF-associated differentially expressed genes (DEGs) and constructed a weighted gene co-expression network (WGCNA). Vascular aging-related targets were retrieved from GeneCards (n = 16,243). Consensus genes (CGs) were derived by intersecting DEGs, WGCNA hub genes, and VA-related targets. Functional enrichment, machine learning prioritization (LASSO regression, Random Forest, and SHAP-XGBoost), and network analysis (GeneMANIA) were applied to identify potential regulators. Top candidates were experimentally validated using qPCR in doxorubicin-induced rat primary vascular smooth muscle cells and human VSMC cell line for the VA model, and H9C2 cardiomyoblast injury model for HF. Further validation was performed in a mouse model of doxorubicin-induced HF, assessing cardiac function by echocardiography, myocardial fibrosis by Masson’s trichrome staining, and vascular aging markers (P16, P21) by qPCR. Results: We identified 272 CGs enriched in cGMP-PKG signaling, cytoskeletal regulation, and PPAR pathways. Machine learning prioritized 12 core genes, with HMOX2 as the top predictor (AUC = 0.978). qPCR analysis confirmed upregulation of HMOX2, S1PR3, and SERPINA3 in doxorubicin-treated rat primary vascular smooth muscle cells, human VSMC cell line, and H9C2 cardiomyoblasts compared to controls (P < 0.05). In the mouse model, doxorubicin administration induced significant cardiac dysfunction and myocardial fibrosis, accompanied by elevated expression of senescence markers P16 and P21 in vascular tissues. These findings collectively suggest that these genes may play important roles in VA-HF comorbidity (P < 0.05).",
  "abstract_shown": true,
  "affiliations": [
    "Guangzhou University of Chinese Medicine, Guangzhou, China",
    "The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China",
    "Shunde Hospital of Guangzhou University of Chinese Medicine, Foshan, China",
    "The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China",
    "State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong, China"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jinze Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Guiting Zhou"
    },
    {
      "affs": [
        2
      ],
      "name": "Qiaochu Wang"
    },
    {
      "affs": [
        3
      ],
      "name": "Zhixuan Song"
    },
    {
      "affs": [
        4
      ],
      "name": "Jiantao Liu"
    },
    {
      "name": "Changzao Shen"
    },
    {
      "name": "Chuanjin Luo"
    },
    {
      "name": "Dawei Wang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2qm52nmjsp583.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pone.0357886",
  "fulltext_url": null,
  "id": "2qm52nmjsp583",
  "issns": [
    "1932-6203"
  ],
  "landing_url": "https://doi.org/10.1371/journal.pone.0357886",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2705|Cardiac Fibrosis and Remodeling"
    ],
    [
      "plos",
      "/Biology and life sciences/Anatomy/Biological tissue/Muscle tissue/Muscle cells/Smooth muscle cells"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Biomarkers"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Nucleic acids/RNA/Non-coding RNA/Small interfering RNA"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Muscle cells/Smooth muscle cells"
    ],
    [
      "plos",
      "/Biology and life sciences/Developmental biology/Organism development/Aging/Senescence"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Gene expression"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Gene expression/Gene regulation/Small interfering RNA"
    ],
    [
      "plos",
      "/Biology and life sciences/Physiology/Physiological processes/Aging/Senescence"
    ],
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      "plos",
      "/Computer and information sciences/Artificial intelligence/Machine learning"
    ],
    [
      "plos",
      "/Medicine and health sciences/Anatomy/Biological tissue/Muscle tissue/Muscle cells/Smooth muscle cells"
    ],
    [
      "plos",
      "/Medicine and health sciences/Cardiology/Heart failure"
    ],
    [
      "plos",
      "/Research and analysis methods/Animal studies/Experimental organism systems/Animal models/Mouse models"
    ],
    [
      "plos",
      "/Research and analysis methods/Animal studies/Experimental organism systems/Model organisms/Mouse models"
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      "plos",
      "/Research and analysis methods/Model organisms/Mouse models"
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  "openalex": "W7213351003",
  "pdf_url": "https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0357886&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-15",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/2qm52nmjsp583.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:49Z",
      "native_id": "10.1371/journal.pone.0357886",
      "source": "plos",
      "url": "https://doi.org/10.1371/journal.pone.0357886"
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  "subjects": [
    {
      "field": "biochemistry",
      "origin": "plos:gene expression",
      "subfield": "molecular-biology"
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    {
      "field": "medicine",
      "origin": "plos:anatomy",
      "subfield": "physiology"
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  "title": "HMOX2-driven crosstalk between vascular aging and heart failure: A multimodal bioinformatics and explainable machine learning approach with experimental validation",
  "title_text": "HMOX2-driven crosstalk between vascular aging and heart failure: A multimodal bioinformatics and explainable machine learning approach with experimental validation",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:49Z",
  "url": "https://research.draconitic.com/paper/2qm52nmjsp583",
  "venue": "PLOS One",
  "versions": []
}