{
  "abstract": "Background: Atherosclerotic cardiovascular disease can progress despite intensive lipid lowering, highlighting the need to identify local mechanisms that remodel established plaques. Intermittent fasting may engage metabolic, circadian, and immune pathways relevant to this process.\n\nMethods: We used genome-wide association study structural equation modeling to construct circulatory plaque burden (CPB) and integrated multi-omic data to prioritize candidate pathways. We then tested intermittent fasting in a baseline-controlled Ldlr⁻/⁻ mouse induction–intervention model and evaluated the BMAL1–MERTK efferocytosis axis in macrophages.\n\nResults: Systems-genetic analyses linked systemic atherosclerotic burden to nutrient-response, circadian, and efferocytosis-related pathways. In mice, intermittent fasting reduced plaque size relative to both the ad libitum-fed and week-14 Baseline groups and improved structural features of plaque stability without additional endpoint lipid lowering. Aortic and single-cell analyses prioritized macrophage BMAL1–MERTK signaling. BMAL1 activated the Mertk promoter and occupied the tested promoter region. Mertk re-expression rescued the efferocytosis defect caused by Bmal1 knockdown, whereas MERTK inhibition reversed the benefit of BMAL1 overexpression.\n\nConclusions: In this mouse model, intermittent fasting promoted remodeling of established atherosclerotic plaques, with macrophage BMAL1–MERTK signaling and efferocytosis identified as contributing mechanisms. These findings provide mechanistic insight and highlight this lifestyle-linked axis as a candidate for future translational investigation alongside established lipid-lowering therapy.\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12964-026-03140-3.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Cardiology, Division of Life Sciences and Medicine, the First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui 230026 China",
    "Department of Cardiology, Affiliated Anhui Provincial Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui 230032 China",
    "Department of Anesthesiology, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui 230026 China",
    "Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515 China",
    "Department of Physiology, Faculty of Basic Medical Sciences, Hubei Key Laboratory of Embryonic Stem Cell Research, Hubei University of Medicine, Shiyan, Hubei 442000 China",
    "State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University, Tianjin, 300071 China",
    "College of Food and Biological Engineering, Hefei University of Technology, Hefei, Anhui 230601 China",
    "Anhui Institute of Cardiovascular Disease, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui 230026 China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Zian Feng"
    },
    {
      "affs": [
        1
      ],
      "name": "Zhiheng Xia"
    },
    {
      "affs": [
        0
      ],
      "name": "Hui Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Chong Fan"
    },
    {
      "affs": [
        2
      ],
      "name": "Zhenxiao Ma"
    },
    {
      "affs": [
        3
      ],
      "name": "Mengyao Wang"
    },
    {
      "affs": [
        4
      ],
      "name": "Ke Gong"
    },
    {
      "affs": [
        5
      ],
      "name": "Baofa Sun"
    },
    {
      "affs": [
        6
      ],
      "name": "Shuang Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yajun Duan",
      "orcid": "0000-0002-3880-9070"
    },
    {
      "affs": [
        0
      ],
      "name": "Buchun Zhang"
    },
    {
      "affs": [
        0,
        7
      ],
      "name": "Zequn Yin"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6zj3gdvkbwe1j.bib",
  "cited_by": 0,
  "doi": "10.1186/s12964-026-03140-3",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13741550/",
  "id": "6zj3gdvkbwe1j",
  "issns": [
    "1478-811X"
  ],
  "landing_url": "https://doi.org/10.1186/s12964-026-03140-3",
  "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": [
    [
      "heading",
      "Research"
    ],
    [
      "openalex",
      "2737|Dietary Effects on Health"
    ]
  ],
  "openalex": "W7202159178",
  "pdf_url": null,
  "pmcid": "PMC13741550",
  "pmid": "42995598",
  "published": "2026-08-11",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/6zj3gdvkbwe1j.ris",
  "sources": [
    {
      "first_seen": "2026-11-10T12:22:35Z",
      "native_id": "PMC13741550",
      "source": "pmc",
      "url": "https://doi.org/10.1186/s12964-026-03140-3"
    }
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2737|Dietary Effects on Health",
      "subfield": "physiology"
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  ],
  "title": "Intermittent fasting promotes plaque regression and activates the BMAL1–MERTK efferocytosis axis",
  "title_text": "Intermittent fasting promotes plaque regression and activates the BMAL1–MERTK efferocytosis axis",
  "type": "peer-reviewed",
  "updated_at": "2026-11-10T12:22:35Z",
  "url": "https://research.draconitic.com/paper/6zj3gdvkbwe1j",
  "venue": "Cell Communication and Signaling : CCS",
  "versions": []
}