{
  "abstract": "Background\n\nFerroptosis, an iron-dependent form of regulated cell death, is implicated in vascular injury, but how immune-related proteins modulate ferroptosis and cerebral atherosclerosis (CeA) remains unclear.Methods\n\nWe performed multi-step Mendelian randomization (MR) integrating plasma proteomics, single-cell eQTL, and FinnGen CeA GWAS data. Mediation MR quantified the role of the ferroptosis regulator FTMT. Cell-type-specific MR was conducted across 14 immune subtypes. Functional enrichment and RT-qPCR of clinical blood samples validated findings.Results\n\nFour immune proteins (KIR2DL3, HLA-E, LTA, MICB) were identified as causal risk factors for CeA, acting primarily by downregulating FTMT (all β₁ < 0, P < 0.001). Mediation analysis revealed FTMT explained up to 53% of the immune protein effect. Single-cell MR demonstrated striking cell-type specificity for MICB: higher MICB in NK cells and IgJ⁺ B cells was strongly associated with CeA risk (e.g., β = 0.90, P = 4.3 × 10⁻⁶), while higher MICB in dendritic cells was protective (β = - 0.57, P = 2.1 × 10⁻³⁰). In clinical samples, RT-qPCR confirmed reduced FTMT expression, and plasma ELISA showed elevated circulating LTA, soluble MICB, and soluble HLA-E in CeA patients. Network analysis highlighted NK cell cytotoxicity as a central pathway.Conclusions\n\nIn summary, our study demonstrates that four immune-related proteins, including MICB, promote cerebral atherosclerosis by downregulating the ferroptosis-protective factor FTMT. Importantly, single-cell MR reveals that MICB acts as a risk factor for CeA specifically in NK cells and plasma cells, providing new mechanistic insight into cell-type-dependent immune regulation of vascular disease.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Clinical laboratory, Shandong Provincial Third Hospital, Shandong University, No.11 Middle Wuyingshan Road, Tianqiao District, Jinan, 250031, Shandong, People's Republic of China. dg730@163.com.",
    "School of Nursing and Rehabilitation, Shandong University, Jinan, 250012, Shandong, People's Republic of China.",
    "Jinan Vocational College of nursing, Jinan, 250102, Shandong, People's Republic of China.",
    "Shandong University of Traditional Chinese Medicine, Jinan, 250014, Shandong China, People's Republic of China.",
    "Department of Clinical laboratory, Shandong Provincial Third Hospital, Shandong University, No.11 Middle Wuyingshan Road, Tianqiao District, Jinan, 250031, Shandong, People's Republic of China.",
    "Department of Clinical laboratory, Shandong Provincial Third Hospital, Shandong University, No.11 Middle Wuyingshan Road, Tianqiao District, Jinan, 250031, Shandong, People's Republic of China. zxw15288869381@163.com."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yonggang Dai"
    },
    {
      "affs": [
        1
      ],
      "name": "Ye Liu"
    },
    {
      "affs": [
        2
      ],
      "name": "Yunjun Yan"
    },
    {
      "affs": [
        3
      ],
      "name": "Haoran Ji"
    },
    {
      "affs": [
        4
      ],
      "name": "Hongya Wang"
    },
    {
      "affs": [
        5
      ],
      "name": "Xuewei Zhuang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/31pddt4hr2a54.bib",
  "cited_by": 0,
  "doi": "10.1186/s13148-026-02212-y",
  "fulltext_url": "https://europepmc.org/articles/PMC13700353",
  "id": "31pddt4hr2a54",
  "issns": [
    "1868-7083"
  ],
  "landing_url": "https://europepmc.org/article/MED/42928267",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2403|Atherosclerosis and Cardiovascular Diseases"
    ]
  ],
  "openalex": "W7171746463",
  "pdf_url": "https://europepmc.org/articles/PMC13700353?pdf=render",
  "pmcid": "PMC13700353",
  "pmid": "42928267",
  "published": "2026-07-29",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/31pddt4hr2a54.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:20Z",
      "native_id": "MED:42928267",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42928267"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Atherosclerosis and Cardiovascular Diseases",
      "subfield": "immunology"
    }
  ],
  "title": "Multi-omics analysis reveals MICB promotes cerebral atherosclerosis through FTMT suppression in NK and plasma cells.",
  "title_text": "Multi-omics analysis reveals MICB promotes cerebral atherosclerosis through FTMT suppression in NK and plasma cells.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:20Z",
  "url": "https://research.draconitic.com/paper/31pddt4hr2a54",
  "venue": "Clinical epigenetics",
  "versions": []
}