{
  "abstract": "Connections between vascular and neurocognitive diseases are emerging but remain poorly defined. Cognitive impairment is increasingly recognized in pulmonary hypertension (PH), a disease traditionally viewed as limited to the heart and lungs. Given that inflammation is shared by PH and neurodegenerative diseases, we investigated its role in driving brain and cognitive deficits in PH. Using structural and functional MRI data from UK Biobank (N = 248 PH) and a prospective validation cohort, we identified reduced cerebellar white matter volume, thinner frontal gyri, and weakened cerebellar-frontal connectivity in patients with PH but not in other heart or lung diseases. These changes were accompanied by worsened executive function and processing speed. Olink proteomics and targeted genomics linked inflammatory plasma proteins and a PH-associated nuclear receptor coactivator 7 (NCOA7) single nucleotide polymorphism, rs11154337, to these deficits. PH cerebellum showed increased microglial activation and white matter derangement. In PH mice, Ncoa7 deficiency worsened cerebellar inflammation and atrophy. Microglial functional assays, cerebellar single-nucleus RNA sequencing, and spatial transcriptomic analyses further implicated Ncoa7-dependent lysosomal, inflammatory, and cell-specific mechanisms of cerebellar pathobiology. These findings identify NCOA7-linked inflammatory dysfunction in the cerebellar-frontal axis in PH, redefining this disease with neurologic consequences and thus offering neural targets for diagnostic, prognostic, and therapeutic development.",
  "abstract_shown": true,
  "affiliations": [
    "Center for Pulmonary Vascular Biology and Medicine, Pittsburgh Heart, Lung, and Blood Vascular Medicine Institute, Division of Cardiology, Department of Medicine",
    "Department of Computational and Systems Biology; and",
    "McGowan Institute for Regenerative Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.",
    "Department of Anesthesiology and Perioperative Medicine, Division of Molecular Medicine, University of California, Los Angeles, Los Angeles, California, USA.",
    "Institute for Lung Health, Department of Internal Medicine, German Center for Lung Research (DZL), Cardio-pulmonary Institute (CPI), Justus Liebig University, Giessen, Germany.",
    "Max Planck Institute for Heart and Lung Research, DZL, CPI, Bad Nauheim, Germany.",
    "Cellular and Molecular Pathology Graduate Program, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.",
    "Heart and Vascular Institute, University of Pittsburgh Medical Center (UPMC), Pittsburgh, Pennsylvania, USA.",
    "Department of Critical Care Medicine",
    "Department of Psychiatry",
    "Department of Radiology, and",
    "Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.",
    "Pittsburgh Veteran’s Affairs Research Center, Pittsburgh, Pennsylvania, USA.",
    "PAH Research Group, Institut Universitaire de Cardiologie et Pneumologie de Québec Research Center, Department of Medicine, Université Laval, Quebec City, Québec, Canada.",
    "Department of Electrical and Computer Engineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.",
    "Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 30,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Satoshi Okawa"
    },
    {
      "affs": [
        0
      ],
      "name": "Yinan Shi"
    },
    {
      "affs": [
        3
      ],
      "name": "Somanshu Banerjee"
    },
    {
      "affs": [
        0
      ],
      "name": "Yi Yin Tai",
      "orcid": "0000-0003-3674-0783"
    },
    {
      "affs": [
        4
      ],
      "name": "Jamal Nabhanizadeh"
    },
    {
      "affs": [
        5
      ],
      "name": "Stefan Guenther"
    },
    {
      "affs": [
        0
      ],
      "name": "Anisha N. Shah"
    },
    {
      "affs": [
        0,
        6
      ],
      "name": "Siyi Jiang"
    },
    {
      "affs": [
        7
      ],
      "name": "Timothy Kim"
    },
    {
      "affs": [
        0
      ],
      "name": "Yassmin Al Aaraj"
    },
    {
      "affs": [
        8
      ],
      "name": "Caroline Pidro"
    },
    {
      "affs": [
        0
      ],
      "name": "Metin Aytekin"
    },
    {
      "affs": [
        9
      ],
      "name": "Omolara Fatukasi"
    },
    {
      "affs": [
        0
      ],
      "name": "Nishita Kalepalli"
    },
    {
      "affs": [
        10
      ],
      "name": "Joseph Mettenburg"
    },
    {
      "affs": [
        8
      ],
      "name": "Timothy D. Girard"
    },
    {
      "affs": [
        9
      ],
      "name": "James T. Becker"
    },
    {
      "affs": [
        11,
        12
      ],
      "name": "Kathiravan Kaliyappan"
    },
    {
      "affs": [
        11,
        12
      ],
      "name": "Shanshan Song"
    },
    {
      "affs": [
        13
      ],
      "name": "Sandra Breuils-Bonnet"
    },
    {
      "affs": [
        13
      ],
      "name": "Steeve Provencher",
      "orcid": "0000-0001-7535-9972"
    },
    {
      "affs": [
        4,
        13
      ],
      "name": "Sébastien Bonnet"
    },
    {
      "affs": [
        14
      ],
      "name": "Theodore Huppert"
    },
    {
      "affs": [
        0
      ],
      "name": "Lloyd D. Harvey",
      "orcid": "0000-0001-5934-9934"
    },
    {
      "affs": [
        15
      ],
      "name": "Seyed Mehdi Nouraie"
    },
    {
      "affs": [
        4,
        5,
        13
      ],
      "name": "Rajkumar Savai",
      "orcid": "0000-0003-1538-2091"
    },
    {
      "affs": [
        11,
        12
      ],
      "name": "Dandan Sun"
    },
    {
      "affs": [
        3
      ],
      "name": "Soban Umar"
    },
    {
      "affs": [
        4,
        5,
        13
      ],
      "name": "Soni S. Pullamsetti"
    },
    {
      "affs": [
        0,
        7
      ],
      "name": "Stephen Y. Chan",
      "orcid": "0000-0002-9520-7527"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8zar7ghxnmswv.bib",
  "cited_by": 1,
  "doi": "10.1172/jci195110",
  "fulltext_url": "https://europepmc.org/articles/PMC13722401",
  "id": "8zar7ghxnmswv",
  "issns": [
    "0021-9738",
    "1558-8238"
  ],
  "landing_url": "https://europepmc.org/article/MED/42969225",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "2740|Pulmonary Hypertension Research and Treatments"
    ]
  ],
  "openalex": "W7225064535",
  "pdf_url": "https://europepmc.org/articles/PMC13722401?pdf=render",
  "pmcid": "PMC13722401",
  "pmid": "42969225",
  "published": "2026-11-02",
  "publisher": "American Society for Clinical Investigation",
  "ris": "https://research.draconitic.com/paper/8zar7ghxnmswv.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T15:20:53Z",
      "native_id": "MED:42969225",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42969225"
    },
    {
      "first_seen": "2026-11-04T12:22:00Z",
      "native_id": "PMC13722401",
      "source": "pmc",
      "url": "https://doi.org/10.1172/jci195110"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2740|Pulmonary Hypertension Research and Treatments",
      "subfield": "general"
    }
  ],
  "title": "Cerebellar and frontal lobe alterations in pulmonary hypertension implicate an inflammatory lung vascular/brain axis.",
  "title_text": "Cerebellar and frontal lobe alterations in pulmonary hypertension implicate an inflammatory lung vascular/brain axis.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T12:20:12Z",
  "url": "https://research.draconitic.com/paper/8zar7ghxnmswv",
  "venue": "The Journal of clinical investigation",
  "versions": []
}