{
  "abstract": "Background: Coronary artery aneurysm is a major cardiovascular complication of Kawasaki disease (KD). The phenotype switch of vascular smooth muscle cells (VSMCs) plays a crucial role in pathological vascular wall remodeling in KD; however, the molecular mechanisms driving this process remain incompletely understood. Although the SPARC protein family has been implicated in various vascular diseases, the role of specific SPARC family members in mediating VSMC phenotypic transition during KD-associated vasculitis remains unknown. Here, we investigated the function and mechanistic role of SPOCK2, a SPARC family member, in vascular wall homeostasis under KD-induced inflammatory stress.\n\nMethods: SPOCK2 transcript expression was evaluated in public transcriptomic datasets and clinical KD cohorts. To model KD vasculitis in vivo , mice were challenged with Candida albicans water-soluble fraction (CAWS). Adeno-associated virus (AAV)2/9-mediated gene transfer was employed for targeted in vivo overexpression of SPOCK2 in mouse aortas. VSMC phenotypic transition, vascular remodeling, extracellular matrix (ECM) integrity, and local cytokine production were assessed using immunofluorescence, RNA sequencing, quantitative RT-PCR, and co-immunoprecipitation assays to delineate SPOCK2–MMP2 structural and functional interactions.\n\nResults: Transcriptional profiling of clinical KD cohorts revealed that SPOCK2 is consistently downregulated in the acute phase of the disease. In murine KD vasculitis models, SPOCK2 expression was notably depleted in both aortic root and abdominal aorta, correlating with severe vascular inflammation and aneurysm formation. Targeted in vivo overexpression of SPOCK2 via AAV2/9 effectively restored the contractile VSMC phenotype, thereby attenuating vasculitis and preventing abdominal aortic aneurysm formation. Mechanistically, SPOCK2 acts as a specific endogenous inhibitor of MMP2. Through physical interaction, SPOCK2 binds to MMP2, hindering its enzymatic activation. In the inflammatory microenvironment of KD, the pathological loss of SPOCK2 leads to unchecked MMP2 activity, promoting uncontrolled extracellular matrix degradation and pathogenic contractile-to-synthetic transition of VSMCs.\n\nConclusion: Our findings establish SPOCK2 as a novel protective factor in vascular wall homeostasis and a potential candidate for preventive strategies targeting vascular remodeling and systemic vasculitis in Kawasaki disease.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Cardiology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University",
    "Department of Cardiology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Children and Adolescents’ Health and Diseases",
    "School of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College",
    "Department of Gynecology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University",
    "Department of Internal Medicine, Kirk Kerkorian School of Medicine at the University of Nevada"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Xiao Xu"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Yucong Wei"
    },
    {
      "affs": [
        1
      ],
      "name": "Min Wang"
    },
    {
      "affs": [
        1
      ],
      "name": "Jiahui Liu"
    },
    {
      "affs": [
        1
      ],
      "name": "Ting Zhao"
    },
    {
      "affs": [
        3
      ],
      "name": "Xian Ma"
    },
    {
      "affs": [
        0
      ],
      "name": "Tielong Chen"
    },
    {
      "affs": [
        4
      ],
      "name": "Buddhadeb Dawn"
    },
    {
      "affs": [
        1
      ],
      "name": "Fangqi Gong"
    },
    {
      "affs": [
        0
      ],
      "name": "Lin Zhao"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9vz4w2nrxm3y8.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1902009",
  "fulltext_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1902009/full",
  "id": "9vz4w2nrxm3y8",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1902009/full",
  "language": "en",
  "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": [
    [
      "lcc",
      "RC581-607"
    ],
    [
      "openalex",
      "2746|Kawasaki Disease and Coronary Complications"
    ]
  ],
  "openalex": "W7223339670",
  "pdf_url": "https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1902009/pdf",
  "pmcid": "PMC13739779",
  "pmid": "42996707",
  "published": "2026-10-23",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/9vz4w2nrxm3y8.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:17Z",
      "native_id": "10.3389/fimmu.2026.1902009",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1902009/full"
    },
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      "url": "https://doi.org/10.3389/fimmu.2026.1902009"
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      "url": "https://europepmc.org/article/MED/42996707"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2746|Kawasaki Disease and Coronary Complications",
      "subfield": "surgery"
    }
  ],
  "title": "SPOCK2-mediated phenotype switch of vascular smooth muscle cells contributes to aortic aneurysm in Kawasaki disease",
  "title_text": "SPOCK2-mediated phenotype switch of vascular smooth muscle cells contributes to aortic aneurysm in Kawasaki disease",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T15:20:34Z",
  "url": "https://research.draconitic.com/paper/9vz4w2nrxm3y8",
  "venue": "Frontiers in Immunology",
  "versions": []
}