{
  "abstract": "The requirement and molecular contribution of acute high-dose aspirin (ASA) in the treatment of Kawasaki disease (KD) remain clinically controversial. This study aimed to investigate the dose-dependent mechanism and pharmacodynamics of adjunctive ASA in an experimental KD mouse model. Male C57BL/6 mice were injected with Lactobacillus casei cell wall extract (LCWE; 100 µg/day, Days 1–7) to induce systemic coronary arteritis. On Day 14, mice received intravenous immunoglobulin (IVIG) (2 g/kg, i.p.) monotherapy (G3) or IVIG combined with High-dose (100 mg/kg; G4), Medium-dose (50 mg/kg; G5), or Low-dose ASA (5 mg/kg; G6) daily via oral gavage for 3 days (Days 14–16), followed by a 5-day drug washout until sacrifice on Day 21. Coronary vasculitis and internal elastic lamina integrity were quantified using H&E and Verhoeff–Van Gieson (VVG) staining. Heart tissue activation of p-nuclear factor kappa-B (NF-κB) and downstream matrix metalloproteinance-9 (MMP-9) expression were evaluated by Western blot. High-dose ASA combined with IVIG (G4) achieved statistically superior suppression of upstream NF-κB phosphorylation (p-NF-κB/NF-κB ratio) and perivascular leukocyte infiltration compared to IVIG monotherapy (G3) (p < 0.05). This acute upstream blockade directly preserved arterial wall architecture, with G4 demonstrating near-baseline structural restoration of the internal elastic lamina on VVG scoring (G4 vs. G3, p < 0.05). Following the 5-day drug washout, downstream MMP-9 expression in G4 converged with G3 levels due to pharmacodynamic waning, whereas suboptimal mid/low-dose ASA regimens (G5/G6) displayed lingering MMP-9 elevation, indicating persistent low-grade matrix remodeling. Acute high-dose ASA provides a non-redundant, synergistic anti-inflammatory effect alongside IVIG to prevent early elastolysis. Maintaining adequate acute ASA dose followed by careful post-withdrawal tapering is vital to prevent delayed arterial wall remodeling and coronary aneurysm progression.",
  "abstract_shown": true,
  "affiliations": [
    "Congenital Structural Heart Disease Center, Department of Pediatrics, Kaohsiung Veterans General Hospital, 386 Ta-Chung 1st Road, Kaohsiung 813, Taiwan",
    "Department of Nursing, Fooyin University, Kaohsiung 831, Taiwan",
    "Zuoying Armed Forces General Hospital, Kaohsiung 813, Taiwan",
    "Department of Respiratory Therapy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan",
    "Department of Pediatrics and Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan",
    "College of Medicine, Chang Gung University, Taoyuan 333, Taiwan",
    "Aging and Diseases Prevention Research Center, Department of Medical Laboratory Science and Biotechnology, Fooyin University, Kaohsiung 831, Taiwan",
    "Department of Pediatrics, China Medical University Children’s Hospital, Taichung 404, Taiwan",
    "School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Kuang-Jen Chien"
    },
    {
      "affs": [
        1
      ],
      "name": "Shih-Hui Huang"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Wei-De Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Chun-Kuei Huang"
    },
    {
      "affs": [
        3,
        4,
        5
      ],
      "name": "Ho-Chang Kuo",
      "orcid": "0000-0002-3295-2984"
    },
    {
      "affs": [
        6
      ],
      "name": "Yao-Tsung Yeh",
      "orcid": "0000-0002-7780-7983"
    },
    {
      "affs": [
        0
      ],
      "name": "Chu-Chuan Lin"
    },
    {
      "affs": [
        7
      ],
      "name": "Kai-Sheng Hsieh"
    },
    {
      "affs": [
        0,
        8
      ],
      "name": "Ken-Pen Weng"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1614n8wfbahfy.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27219783",
  "fulltext_url": null,
  "id": "1614n8wfbahfy",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/21/9783",
  "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": "2026-10-30",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/1614n8wfbahfy.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:20:54Z",
      "native_id": "10.3390/ijms27219783",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/21/9783"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "issn:1422-0067",
      "subfield": "general"
    }
  ],
  "title": "Evaluation of Dose-Dependent Efficacy and Mechanisms of Aspirin Combined with Intravenous Immunoglobulin in a Murine Model of Kawasaki Disease Vasculitis",
  "title_text": "Evaluation of Dose-Dependent Efficacy and Mechanisms of Aspirin Combined with Intravenous Immunoglobulin in a Murine Model of Kawasaki Disease Vasculitis",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T00:20:52Z",
  "url": "https://research.draconitic.com/paper/1614n8wfbahfy",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}