{
  "abstract": "Plaque heterogeneity underlies the propensity of atherosclerotic lesions to rupture and trigger cardiovascular events. Most proteomic studies examine bulk changes, obscuring key spatial differences in protein abundance. We report a high-resolution spatial proteomics workflow exploring the molecular landscape of human plaques and a murine myocardium. By combining laser capture microdissection with high-sensitivity ion-mobility mass spectrometry, spatial profiling of cellular and extracellular matrix (ECM) proteomes was achieved. Over 2700 proteins were detected from 50,000 μm2 areas, revealing substantial intraplaque heterogeneity across distinct regions (lipid-rich, media, shoulder, necrotic core, intima) and distance from the artery lumen. Inverse correlations between proteases (cathepsin B) and core structural ECM proteins (perlecan, HSPG2) indicated active ECM remodeling. Analysis of media layers indicated distinct protein signatures associated with smooth muscle contraction and cell–cell communication. Blood coagulation signatures, including platelet degranulation and fibrin formation, were enriched at the intima. Inflammatory (clusters of differentiation 4/68, CD4/CD68; vascular cell adhesion molecule 1, VCAM1) and vascular damage markers (tenascin-C, TNC) were enriched in shoulder regions. The necrotic core was dominated by blood proteins, consistent with intraplaque hemorrhage. This workflow resolves proteomic changes over ∼200 μm distances, providing unprecedented insights into plaque morphology and offers a powerful tool for elucidating plaque biology.",
  "abstract_shown": true,
  "affiliations": [
    "University of Copenhagen , , ,",
    "Department of Biomedical Sciences, Panum Institute, University of Copenhagen, Denmark",
    "Copenhagen University Hospital - Rigshospitalet , , ,",
    "Department of Vascular Surgery, Heart Centre, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark",
    "Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark",
    "Capital Region of Denmark , , ,",
    "Copenhagen Academy for Medical Education and Simulation (CAMES), Capital Region of Denmark, Copenhagen, Denmark",
    "Lund University , , Clinical Research Centre , ,"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Kathrine V. Jokumsen",
      "orcid": "0009-0008-1058-558X"
    },
    {
      "affs": [
        2,
        0,
        1,
        3
      ],
      "name": "Lasse G. Lorentzen",
      "orcid": "0000-0002-0895-5739"
    },
    {
      "affs": [
        2,
        0,
        4,
        3
      ],
      "name": "Karin Yeung",
      "orcid": "0000-0002-9194-4650"
    },
    {
      "affs": [
        2,
        0,
        4,
        3
      ],
      "name": "Timothy Andrew Resch",
      "orcid": "0000-0001-8407-8216"
    },
    {
      "affs": [
        5,
        2,
        0,
        6,
        4,
        3
      ],
      "name": "Jonas Eiberg",
      "orcid": "0000-0002-7930-3842"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Michael J. Davies",
      "orcid": "0000-0002-5196-6919"
    },
    {
      "affs": [
        7,
        0,
        1
      ],
      "name": "Luke F. Gamon",
      "orcid": "0000-0001-7894-8035"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1h44shvzf4a7d.bib",
  "cited_by": 5,
  "doi": "10.1021/acs.jproteome.6c00011",
  "fulltext_url": null,
  "id": "1h44shvzf4a7d",
  "issns": [
    "1535-3893",
    "1535-3907"
  ],
  "landing_url": "https://doi.org/10.1021/acs.jproteome.6c00011",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1607|Advanced Proteomics Techniques and Applications"
    ]
  ],
  "openalex": "W4411463077",
  "pdf_url": null,
  "pmcid": null,
  "pmid": "42695902",
  "published": "2026-08-19",
  "publisher": "American Chemical Society",
  "ris": "https://research.draconitic.com/paper/1h44shvzf4a7d.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T13:20:28Z",
      "native_id": "W4411463077",
      "source": "openalex",
      "url": "https://doi.org/10.1021/acs.jproteome.6c00011"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:1607|Advanced Proteomics Techniques and Applications",
      "subfield": "physical"
    }
  ],
  "title": "Spatial Proteomics of the Human Atherosclerotic Microenvironment Reveals Heterogeneity in Intraplaque Proteomes and Extracellular Matrix Remodeling",
  "title_text": "Spatial Proteomics of the Human Atherosclerotic Microenvironment Reveals Heterogeneity in Intraplaque Proteomes and Extracellular Matrix Remodeling",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T13:20:39Z",
  "url": "https://research.draconitic.com/paper/1h44shvzf4a7d",
  "venue": "Journal of Proteome Research",
  "versions": []
}