{
  "abstract": "Background: Despite advances in therapy, pulmonary arterial hypertension (PAH) remains progressive with poor survival. Although dysregulation of bone morphogenetic protein (BMP) signalling is central to PAH, key modulators of this pathway remain incompletely defined.\n\nObjectives: To identify the role of BMP3 in pulmonary vascular homeostasis and PAH.\n\nMethods: BMP3 expression was assessed in experimental pulmonary hypertension and in pulmonary vascular cells and plasma from PAH patients. In vitro studies were performed in human pulmonary artery smooth muscle cells (hPASMCs) and endothelial cells (hPAECs). Global and smooth muscle cell-specific Bmp3-deficient mice were generated. Recombinant BMP3 and adeno-associated viruses (AAVs) were used to overexpress BMP3 in animal models of PAH.\n\nResults: BMP3 is predominantly expressed in PASMCs and is consistently downregulated in experimental and human PAH. Secreted BMP3 from PAH-PASMCs and circulating BMP3 levels in PAH patients were significantly reduced. Functionally, PASMC-derived BMP3 inhibited the migration and proliferation of PAH-diseased PAECs. In both global and smooth muscle cell-specific Bmp3-deficient mice, induction of PAH led to significantly exacerbated disease in middle-aged mice. A recombinant BMP3 prevented and reversed PAH in mice. Furthermore, lung-targeted overexpression of BMP3, via AAV1-BMP3, reversed pulmonary vascular remodelling and ameliorated cardiac function in both mice and rats. Mechanistically, BMP3 restored the balance between BMP/SMAD1,5,8 and transforming growth factor (TGF)-β/SMAD2,3 signalling, and decreased the expression of cell cycle genes in PAECs.\n\nConclusions: BMP3 acts as a paracrine regulator of pulmonary vascular homeostasis and may contribute to the modulation of TGF-β/BMP signalling in PAH, highlighting its potential as a therapeutic target.",
  "abstract_shown": true,
  "affiliations": [
    "Fralin Biomedical Research Institute at Virginia Tech Carilion, Roanoke, VA, USA",
    "Icahn School of Medicine at Mount Sinai, New York, NY, USA",
    "Department of Pharmacological Science, Icahn School of Medicine at Mount Sinai, New York, NY, USA",
    "Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA, USA",
    "Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA",
    "Department of Internal Medicine, VTC School of Medicine, Roanoke, VA, USA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Aymen Halouani"
    },
    {
      "affs": [
        0
      ],
      "name": "Eric Mensah"
    },
    {
      "affs": [
        0
      ],
      "name": "Mariem Ben Rhouma"
    },
    {
      "affs": [
        0
      ],
      "name": "Zaujia Athumani"
    },
    {
      "affs": [
        1
      ],
      "name": "Michael G. Katz"
    },
    {
      "affs": [
        0
      ],
      "name": "Seun Imani"
    },
    {
      "affs": [
        0
      ],
      "name": "Samar A. Antar"
    },
    {
      "affs": [
        2
      ],
      "name": "Katherine Jankowski"
    },
    {
      "affs": [
        2
      ],
      "name": "Maryam Mansoori"
    },
    {
      "affs": [
        3
      ],
      "name": "Vicki Rosen"
    },
    {
      "affs": [
        1
      ],
      "name": "Kiyotake Ishikawa"
    },
    {
      "affs": [
        2
      ],
      "name": "Lahouaria Hadri"
    },
    {
      "affs": [
        0,
        4,
        5
      ],
      "name": "Yassine Sassi"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/aggya2qva9y9j.bib",
  "cited_by": 2,
  "doi": "10.1183/13993003.02146-2025",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13735184/",
  "id": "aggya2qva9y9j",
  "issns": [
    "0903-1936",
    "1399-3003"
  ],
  "landing_url": "https://doi.org/10.1183/13993003.02146-2025",
  "language": "en",
  "licence": "CC-BY-NC-4.0",
  "licence_label": "CC BY-NC 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "7"
    ],
    [
      "heading",
      "Original Research Article"
    ],
    [
      "heading",
      "Pulmonary Vascular Disease"
    ],
    [
      "openalex",
      "2740|Pulmonary Hypertension Research and Treatments"
    ]
  ],
  "openalex": "W4411462263",
  "pdf_url": null,
  "pmcid": "PMC13735184",
  "pmid": "42532545",
  "published": "2026-11-05",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/aggya2qva9y9j.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:20:54Z",
      "native_id": "PMC13735184",
      "source": "pmc",
      "url": "https://doi.org/10.1183/13993003.02146-2025"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2740|Pulmonary Hypertension Research and Treatments",
      "subfield": "general"
    }
  ],
  "title": "Paracrine action of bone morphogenetic protein 3 in pulmonary arterial hypertension",
  "title_text": "Paracrine action of bone morphogenetic protein 3 in pulmonary arterial hypertension",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:20:54Z",
  "url": "https://research.draconitic.com/paper/aggya2qva9y9j",
  "venue": "The European Respiratory Journal",
  "versions": []
}