{
  "abstract": "Background: In heart failure (HF), DNA damage caused by various external stressors contributes to cardiac dysfunction through the activation of DNA damage response pathways. To date, no clinical strategies have been established to restore cardiac function by reducing accumulated DNA damage. We previously found that vitamin D improved contractility in lamin A/C (LMNA) p.Q353R–mutant induced pluripotent stem (iPS) cell-derived cardiomyocytes (iPSCMs), but whether this effect extends to other LMNA variants and in vivo models remained uncertain.\n\nObjectives: The objective of the study was to evaluate the association of vitamin D pathway activation with cardiomyocyte phosphorylated histone H2AX (γH2AX) foci and contractile phenotypes in patient-derived iPSCMs and mouse models of HF.\n\nMethods: iPS cell lines were generated from dilated cardiomyopathy patients carrying the LMNA p.R225X mutation, and the effects of vitamin D treatment on γH2AX foci and cardiomyocyte contractility were evaluated. In addition, the effects of the vitamin D analog paricalcitol were evaluated in Lmna p.R225X mice and in a pressure overload mouse model of HF.\n\nResults: Consistent with previous findings, vitamin D treatment reduced γH2AX foci in cardiomyocytes derived from LMNA p.R225X mutant iPS cells through upregulating the expression of DNA repair factors, and improved contractility in these iPSCMs. Furthermore, paricalcitol reduced γH2AX foci and attenuated cardiac dysfunction in both Lmna p.R225X mice and pressure overload HF model mice.\n\nConclusions: Vitamin D pathway activation improved contractile phenotypes across complementary preclinical models and was accompanied by reduced γH2AX foci or related transcriptional changes. These findings support further mechanistic and preclinical investigation.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan",
    "Department of Frontier Cardiovascular Science, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan",
    "Center for Epidemiology and Preventive Medicine, The University of Tokyo Hospital, Bunkyo-ku, Tokyo, Japan",
    "Center for Regenerative Medicine, National Center for Child Health and Development Research Institute, Setagaya-ku, Tokyo, Japan",
    "Department of Systems Developmental Biology, National Center for Child Health and Development Research Institute, Setagaya-ku, Tokyo, Japan",
    "Department of Biodesign, Division of Biofunctional Restoration Institute of Biomaterials and Bioengineering, Science Tokyo, Chiyoda-ku, Tokyo, Japan",
    "Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan",
    "Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Meguro-ku, Tokyo, Japan",
    "Department of Cardiovascular Medicine, Nara Medical University, Kashihara-shi, Nara, Japan",
    "International University of Health and Welfare, Minato-ku, Tokyo, Japan"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 26,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Masamichi Ito"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Manami Katoh"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Masayuki Kubota"
    },
    {
      "affs": [
        0
      ],
      "name": "Masataka Yamasaki"
    },
    {
      "affs": [
        0
      ],
      "name": "Yanfei Zhang"
    },
    {
      "affs": [
        1
      ],
      "name": "Jin Komuro"
    },
    {
      "affs": [
        0
      ],
      "name": "Ayako Tsukihashi"
    },
    {
      "affs": [
        0
      ],
      "name": "Shintaro Yamada"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Toshiyuki Ko"
    },
    {
      "affs": [
        0
      ],
      "name": "Mikako Katagiri"
    },
    {
      "affs": [
        0
      ],
      "name": "Ryo Abe"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Shunsuke Inoue"
    },
    {
      "affs": [
        0
      ],
      "name": "Takashi Hiruma"
    },
    {
      "affs": [
        0
      ],
      "name": "Daigo Nishijo"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Zhehao Dai"
    },
    {
      "affs": [
        0
      ],
      "name": "Hiroyuki Morita"
    },
    {
      "affs": [
        3
      ],
      "name": "Masashi Toyoda"
    },
    {
      "affs": [
        4
      ],
      "name": "Shuji Takada"
    },
    {
      "affs": [
        5
      ],
      "name": "Masashi Ikeuchi"
    },
    {
      "affs": [
        6
      ],
      "name": "Katsuhisa Matsuura"
    },
    {
      "affs": [
        2
      ],
      "name": "Akihiro Umezawa"
    },
    {
      "affs": [
        7
      ],
      "name": "Hiroyuki Aburatani"
    },
    {
      "affs": [
        8
      ],
      "name": "Kenji Onoue"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Seitaro Nomura"
    },
    {
      "affs": [
        0
      ],
      "name": "Norihiko Takeda"
    },
    {
      "affs": [
        1,
        9
      ],
      "name": "Issei Komuro"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0nq15yn2cmx0m.bib",
  "cited_by": 0,
  "doi": "10.1016/j.jacadv.2026.103199",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13699713/",
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  "landing_url": "https://doi.org/10.1016/j.jacadv.2026.103199",
  "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",
      "Heart Failure and Cardiomyopathies"
    ],
    [
      "heading",
      "Original Research"
    ],
    [
      "lcc",
      "RC666-701"
    ],
    [
      "lcc",
      "RC86-88.9"
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      "2705|Cardiomyopathy and Myosin Studies"
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  "pdf_url": "https://www.jacc.org/doi/pdf/10.1016/j.jacadv.2026.103199?download=true",
  "pmcid": "PMC13699713",
  "pmid": "42720657",
  "published": "2026-09-09",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/0nq15yn2cmx0m.ris",
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    {
      "first_seen": "2026-10-30T12:20:17Z",
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      "origin": "openalex:2705|Cardiomyopathy and Myosin Studies",
      "subfield": "cardiovascular"
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  ],
  "title": "Vitamin D Pathway Activation Reduces Cardiomyocyte DNA Damage and Improves Cardiac Contractility in Preclinical Models",
  "title_text": "Vitamin D Pathway Activation Reduces Cardiomyocyte DNA Damage and Improves Cardiac Contractility in Preclinical Models",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:43:15Z",
  "url": "https://research.draconitic.com/paper/0nq15yn2cmx0m",
  "venue": "JACC: Advances",
  "versions": []
}