{
  "abstract": "Programmed cell death ligand-1 (PD-L1) is an immune checkpoint protein expressed in vascular endothelial cells (ECs). In contrast to cancer, our understanding of endothelial PD-L1 in relation to metabolic syndromes and its vascular complications is less studied. For example, its regulation and intrinsic function remain unclear. Here, we showed that endothelial PD-L1 is regulated by leptin receptor signaling in male mice. In particular, endothelial PD-L1 expression is affected by leptin resistance. A lack of leptin receptors leads to PD-L1 downregulation in vascular ECs via posttranslational degradation. To understand the fundamental roles of endothelial PD-L1, RNA interference and selective knockout are employed in human endothelium and animals, respectively. Silencing or deleting endothelial PD-L1 expression delays cell cycle progression and proliferation due to rat sarcoma (RAS)/mitogen-activated protein kinase (MAPK) inactivation. In obesity, endothelial PD-L1 deficiency impairs the EC turnover and worsens the vascular function. Overall, we provide an insight into how endothelial PD-L1 contributes to vascular homeostasis, suggesting its pathophysiological importance in maintaining cellular turnover.",
  "abstract_shown": true,
  "affiliations": [
    "School of Life Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China",
    "State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China",
    "Department of Population Health, School of Nursing and Health Sciences, Hong Kong Metropolitan University, Hong Kong Special Administrative Region, China",
    "Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai 200080, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Yiu Ming Cheung",
      "orcid": "0000-0001-7366-3882"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Hoi Wa Yeung",
      "orcid": "0009-0000-3660-3354"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Chufeng He",
      "orcid": "0009-0004-2195-6615"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Qile Zhang",
      "orcid": "0009-0001-1053-4386"
    },
    {
      "affs": [
        0
      ],
      "name": "Chui Yiu Bamboo Chook",
      "orcid": "0000-0002-1366-6990"
    },
    {
      "affs": [
        2
      ],
      "name": "Gary Tse"
    },
    {
      "affs": [
        3
      ],
      "name": "Yun Liao"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Wing Tak Wong",
      "orcid": "0000-0002-4514-3780"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fc2war6hwf1cm.bib",
  "cited_by": 0,
  "doi": "10.1073/pnas.2609322123",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13732235/",
  "id": "fc2war6hwf1cm",
  "issns": [
    "0027-8424",
    "1091-6490"
  ],
  "landing_url": "https://doi.org/10.1073/pnas.2609322123",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "427"
    ],
    [
      "heading",
      "Biological Sciences"
    ],
    [
      "heading",
      "Physiology"
    ],
    [
      "openalex",
      "2712|Adipokines, Inflammation, and Metabolic Diseases"
    ]
  ],
  "openalex": "W7224664588",
  "pdf_url": null,
  "pmcid": "PMC13732235",
  "pmid": "42956031",
  "published": "2026-10-29",
  "publisher": "National Academy of Sciences",
  "ris": "https://research.draconitic.com/paper/fc2war6hwf1cm.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:22:16Z",
      "native_id": "PMC13732235",
      "source": "pmc",
      "url": "https://doi.org/10.1073/pnas.2609322123"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "heading:Physiology",
      "subfield": "physiology"
    }
  ],
  "title": "Intrinsic function of leptin receptor–regulated endothelial PD-L1",
  "title_text": "Intrinsic function of leptin receptor–regulated endothelial PD-L1",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:22:16Z",
  "url": "https://research.draconitic.com/paper/fc2war6hwf1cm",
  "venue": "Proceedings of the National Academy of Sciences of the United States of America",
  "versions": []
}