{
  "abstract": "BackgroundAtherosclerotic plaque progression couples chronic inflammation to dysregulated cell survival, but the cellular context and regulatory role of endoplasmic reticulum (ER)-associated death responses in human carotid disease remain incompletely resolved.MethodsWe integrated paired bulk transcriptomes from 32 carotid plaque and macroscopically intact tissue pairs, laser-captured macrophages from five ruptured and six stable plaques, whole-plaque transcriptomes from 27 intraplaque-hemorrhage and 16 non-hemorrhage lesions, and single-cell RNA sequencing from three patients with matched atherosclerotic core and proximal adjacent tissue. BCAP31 was evaluated by siRNA-mediated depletion in oxidized low-density lipoprotein (oxLDL)-exposed THP-1-derived macrophages, with PCR, immunofluorescence, ELISA, apoptosis assays, and 4-phenylbutyrate treatment.ResultsPaired bulk analysis showed coordinated increases in apoptosis, ferroptosis, pyroptosis, necroptosis, inflammasome, inflammatory-response, and TNF/NF-κB programs. Ruptured plaque macrophages showed increases in ferroptosis, pyroptosis, and necroptosis scores, whereas intraplaque-hemorrhage plaques showed broader activation across all prespecified programs. Patient-level single-cell pseudobulk analysis localized a directionally consistent increase in BCAP31 to macrophages, although the estimate did not remain significant after transcriptome-wide correction in the three-patient dataset. Cross-sectional state ordering placed higher BCAP31 expression toward plaque-enriched HLA-C1QC, APOC1-SPP1-remodeling, and SPP1-lipid-loaded macrophage states, while predicted macrophage-to-vascular-wall SPP1 signaling increased in all three patient pairs. BCAP31 was also increased in paired plaque, rupture-macrophage, and intraplaque-hemorrhage cohorts and belonged to a plaque-associated coexpression module. In macrophages derived from THP-1 cells and treated with oxLDL, BCAP31 knockdown increased ER-stress transcripts, nuclear DDIT3, inflammatory cytokine expression and release, and Annexin V-positive apoptosis. The chemical chaperone 4-phenylbutyrate attenuated these effects.ConclusionHuman plaque transcriptomics and macrophage perturbation support a stress-adaptive role for BCAP31 in ER-stress-associated inflammation and apoptosis. Increased tissue expression and the adverse effects of depletion indicate that plaque-associated upregulation may reflect a compensatory response.",
  "abstract_shown": true,
  "affiliations": [
    "epartment of Cardiology, Wenzhou Central Hospital, Wenzhou, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yunlong Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Bin Lin"
    },
    {
      "affs": [
        0
      ],
      "name": "Shanjiang Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Jianjian Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "Anwu Huang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/84gqy6w3c4cga.bib",
  "cited_by": 0,
  "doi": "10.3389/fcell.2026.1970662",
  "fulltext_url": "https://www.frontiersin.org/articles/10.3389/fcell.2026.1970662/full",
  "id": "84gqy6w3c4cga",
  "issns": [
    "2296-634X"
  ],
  "landing_url": "https://doi.org/10.3389/fcell.2026.1970662",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "QH301-705.5"
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      "openalex",
      "2403|Atherosclerosis and Cardiovascular Diseases"
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  "pdf_url": "https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2026.1970662/pdf",
  "pmcid": "PMC13740992",
  "pmid": "42997182",
  "published": "2026-10-23",
  "publisher": "Frontiers Media S.A.",
  "ris": "https://research.draconitic.com/paper/84gqy6w3c4cga.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:44:00Z",
      "native_id": "da9d44d77bf046e38b8e30c728c009e6",
      "source": "doaj",
      "url": "https://doi.org/10.3389/fcell.2026.1970662"
    },
    {
      "first_seen": "2026-11-09T15:20:41Z",
      "native_id": "MED:42997182",
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      "url": "https://europepmc.org/article/MED/42997182"
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  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Atherosclerosis and Cardiovascular Diseases",
      "subfield": "immunology"
    }
  ],
  "title": "Integrated human carotid plaque transcriptomics and macrophage perturbation link BCAP31 to endoplasmic reticulum stress, inflammation, and apoptosis",
  "title_text": "Integrated human carotid plaque transcriptomics and macrophage perturbation link BCAP31 to endoplasmic reticulum stress, inflammation, and apoptosis",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T15:20:41Z",
  "url": "https://research.draconitic.com/paper/84gqy6w3c4cga",
  "venue": "Frontiers in Cell and Developmental Biology",
  "versions": []
}