{
  "abstract": "Introduction\n\nDysregulated lipid metabolism and inflammation are two core pathological drivers of atherosclerosis; however, their causal interplay remains incompletely elucidated. Macrophages play a central role in sustaining unresolved inflammation, which is a hallmark of atherosclerosis. Recent single-cell RNA-sequencing studies have revealed phenotypic heterogeneity among macrophages in atherosclerotic lesions, encompassing two key pro-atherogenic subsets: pro-inflammatory and foam cell-forming macrophages. Given that oxidized low-density lipoprotein (oxLDL) is a pivotal pathological factor in atherosclerosis, we investigated whether and how oxLDL drives the reprogramming of macrophages toward a pro-atherogenic phenotype.Methods\n\nTranscriptomic analyses were performed on macrophages exposed to oxLDL, followed by a series of in vitro and ex vivo experiments to characterize the phenotypic, metabolic, and functional changes.Results\n\nWe identified a macrophage phenotype, named oxLDL-activated macrophages (OAMs), which displayed significant molecular and functional similarities to both pro-inflammatory and foam cell-forming macrophages. OxLDL-induced macrophage reprogramming was associated with a metabolic paradigm shift from oxidative phosphorylation to glycolysis, which was abrogated by inhibition of NF-κB activation, accompanied by polarization toward an anti-inflammatory phenotype. Knockdown of ARNT (encoding HIF-1β) recapitulated the effects of NF-κB inhibition, positioning HIF-1β downstream of the NF-κB pathway. Furthermore, inhibition of NF-κB also attenuated oxLDL-induced inflammasome activation and priming for a heightened secondary response, impaired the foam cell-forming capacity of OAMs, and moderately affected efferocytosis.Conclusions\n\nOur findings demonstrate that oxLDL drives macrophage polarization toward a pro-atherogenic (pro-inflammatory and foam cell-prone) phenotype via metabolic rewiring and transcriptional remodeling mediated by HIF-1β-dependent crosstalk between the NF-κB and HIF pathways. This signaling axis may serve as a potential therapeutic target for atherosclerosis.",
  "abstract_shown": true,
  "affiliations": [
    "Laboratory of Cancer Precision Medicine, Institute of Translational Research, The First Hospital of Jilin University, Changchun, Jilin, China.",
    "Jilin Provincial Key Laboratory of Precision Medicine for Age-Related Diseases, Changchun, China.",
    "Department of Neurology, The First Hospital of Jilin University, Changchun, Jilin, China.",
    "Department of Neurology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.",
    "Department of Hematology, The First Hospital of Jilin University, Changchun, Jilin, China.",
    "Department of Hematology and Oncology, Shanghai Jing'an District Zhabei Central Hospital, Shanghai, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Maozhuo Lan"
    },
    {
      "affs": [
        2
      ],
      "name": "Yangyang Zhou"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yue Sun"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Xingcheng Yi"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Mengtuan Long"
    },
    {
      "affs": [
        3
      ],
      "name": "Dirk M Hermann"
    },
    {
      "affs": [
        4
      ],
      "name": "Fengyan Jin"
    },
    {
      "affs": [
        0,
        1,
        5
      ],
      "name": "Yun Dai"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bdnyyqjz3knpt.bib",
  "cited_by": 0,
  "doi": "10.3389/fcvm.2026.1957621",
  "fulltext_url": "https://europepmc.org/articles/PMC13683113",
  "id": "bdnyyqjz3knpt",
  "issns": [
    "2297-055X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42908577",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2403|Atherosclerosis and Cardiovascular Diseases"
    ]
  ],
  "openalex": "W7220840281",
  "pdf_url": "https://europepmc.org/articles/PMC13683113?pdf=render",
  "pmcid": "PMC13683113",
  "pmid": "42908577",
  "published": "2026-10-07",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/bdnyyqjz3knpt.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:53Z",
      "native_id": "MED:42908577",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42908577"
    },
    {
      "first_seen": "2026-10-30T12:20:10Z",
      "native_id": "10.3389/fcvm.2026.1957621",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fcvm.2026.1957621/full"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Atherosclerosis and Cardiovascular Diseases",
      "subfield": "immunology"
    }
  ],
  "title": "OxLDL drives pro-inflammatory and foam cell-prone macrophage reprogramming via NF-κB/HIF-1β-dependent metabolic rewiring.",
  "title_text": "OxLDL drives pro-inflammatory and foam cell-prone macrophage reprogramming via NF-κB/HIF-1β-dependent metabolic rewiring.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:10Z",
  "url": "https://research.draconitic.com/paper/bdnyyqjz3knpt",
  "venue": "Frontiers in cardiovascular medicine",
  "versions": []
}