{
  "abstract": "Background: Circadian rhythms have been implicated in the regulation of cardiovascular physiology and disease. Disruption of circadian signaling has been linked to exaggerated neointimal hyperplasia and delayed endothelial repair. Bmal1, a core component of the molecular clock, plays a critical role in maintaining vascular homeostasis. However, the specific contribution of endothelial cell (EC)-derived Bmal1 to post-injury neointimal hyperplasia remains unclear. This study aims to elucidate the role and mechanisms of EC-derived Bmal1 in vascular restenosis.\n\nMethods and results: EC-specific Bmal1 knockout mice (Bmal1f/f-Tie2Cre+ and Bmal1f/f-Cdh5Cre+) and their littermate controls (Bmal1f/f) were subjected to carotid artery ligation and femoral artery wire injury models. EC-Bmal1 deficiency significantly aggravated neointimal hyperplasia, impaired re-endothelialization, enhanced leukocyte infiltration, and promotes vascular smooth muscle cell (VSMC) phenotypic modulation. Mechanistically, loss of EC-Bmal1 reduced endothelial proliferation, migration, and angiogenic capacity. Moreover, EC-Bmal1 deficiency was associated with activation of NF-κB signaling, leading to upregulated expression and secretion of interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), and other endothelial-derived mediators. IL-6 promotes VSMC phenotypic modulation via the PKA signaling axis, while ICAM-1 facilitated monocyte adhesion through activation of the phosphorylated JNK signaling. These intrinsic and paracrine mechanisms synergistically contributed to vascular remodeling after injury.\n\nConclusions: Our study identifies a protective role of EC-Bmal1 in limiting injury-induced vascular restenosis and suggests that endothelial Bmal1 may represent a potential therapeutic target for preventing restenosis after percutaneous coronary intervention.\n\nGraphical abstract: In wild-type mice with intact endothelial Bmal1 expression, vascular injury induces only moderate ICAM-1 and IL-6 expression, thereby maintaining controlled repair responses. In contrast, in EC-Bmal1-KO mice, endothelial Bmal1 deficiency not only suppresses endothelial proliferation and migration, impairing regeneration, but also drives paracrine NF-κB–mediated upregulation of ICAM-1 and IL-6, which promotes monocyte infiltration, macrophage activation, and VSMC remodeling, collectively exacerbating restenosis\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12964-026-03116-3.",
  "abstract_shown": true,
  "affiliations": [
    "Advanced Institute for Medical Sciences, Dalian Medical University, Dalian, 116044, China.",
    "Health Science Center, East China Normal University, Shanghai, 200241, China. hxu@hsc.ecnu.edu.cn.",
    "College of Basic Medical Sciences, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China.",
    "Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China. heqingyongg@163.com.",
    "Advanced Institute for Medical Sciences, Dalian Medical University, Dalian, 116044, China. lhchen@hsc.ecnu.edu.cn.",
    "Health Science Center, East China Normal University, Shanghai, 200241, China. lhchen@hsc.ecnu.edu.cn."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Qing Liang"
    },
    {
      "affs": [
        1
      ],
      "name": "Hu Xu"
    },
    {
      "affs": [
        0
      ],
      "name": "Ruqiang Yuan"
    },
    {
      "affs": [
        0
      ],
      "name": "Min Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Lei Qian"
    },
    {
      "affs": [
        0
      ],
      "name": "Jiajia Yi"
    },
    {
      "affs": [
        2
      ],
      "name": "Guangrui Yang"
    },
    {
      "affs": [
        3
      ],
      "name": "Qingyong He"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Lihong Chen",
      "orcid": "0000-0001-6370-1865"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cc0a328a0n85h.bib",
  "cited_by": 0,
  "doi": "10.1186/s12964-026-03116-3",
  "fulltext_url": "https://europepmc.org/articles/PMC13726034",
  "id": "cc0a328a0n85h",
  "issns": [
    "1478-811X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42968094",
  "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": [
    [
      "heading",
      "Research"
    ],
    [
      "openalex",
      "2807|Circadian rhythm and melatonin"
    ]
  ],
  "openalex": "W7172398803",
  "pdf_url": "https://europepmc.org/articles/PMC13726034?pdf=render",
  "pmcid": "PMC13726034",
  "pmid": "42968094",
  "published": "2026-08-05",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/cc0a328a0n85h.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T15:20:53Z",
      "native_id": "MED:42968094",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42968094"
    },
    {
      "first_seen": "2026-11-05T12:22:27Z",
      "native_id": "PMC13726034",
      "source": "pmc",
      "url": "https://doi.org/10.1186/s12964-026-03116-3"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2807|Circadian rhythm and melatonin",
      "subfield": "physiology"
    }
  ],
  "title": "Endothelial Bmal1 coordinates intrinsic and paracrine mechanisms to limit post-injury vascular restenosis.",
  "title_text": "Endothelial Bmal1 coordinates intrinsic and paracrine mechanisms to limit post-injury vascular restenosis.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T12:22:05Z",
  "url": "https://research.draconitic.com/paper/cc0a328a0n85h",
  "venue": "Cell communication and signaling : CCS",
  "versions": []
}