{
  "abstract": "Heart failure with preserved ejection fraction (HFpEF) remains a major unmet clinical challenge. Although obesity is common in many HFpEF cohorts from Europe and North America, three Japanese HFpEF cohorts identified hypertension and sympathetic overactivation, rather than obesity, as dominant features. To model these features, we established an HFpEF mouse model in which sympathetic activation induces hypertensive heart disease, while endothelial dysfunction acts as a second hit driving progression to HFpEF. Hypertensive stress rewires cardiac macrophage-derived intercellular signaling, impairing macrophage-to-cardiomyocyte BMP signaling and fatty acid oxidation while enhancing macrophage-to-fibroblast PDGF signaling, thereby promoting metabolic remodeling, inflammation, and fibrosis. ANGPTL2 inhibition preserves macrophage intercellular communication and prevents HFpEF development. These findings identify cardiac macrophage signaling rewiring as a central mechanism linking hypertensive stress to metabolic remodeling and inflammation, revealing a pathogenic pathway for HFpEF in the absence of obesity that is distinct from HFpEF associated with obesity.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 28,
  "authors": [
    {
      "name": "Yuya Kinoshita"
    },
    {
      "name": "Michio Sato",
      "orcid": "0000-0001-9339-1642"
    },
    {
      "name": "Tsuyoshi Kadomatsu",
      "orcid": "0000-0003-3327-6954"
    },
    {
      "name": "Manami Katoh",
      "orcid": "0000-0001-5634-9170"
    },
    {
      "name": "Kazutaka Ikeda"
    },
    {
      "name": "Goro Yoshioka"
    },
    {
      "name": "Yuya Matsue"
    },
    {
      "name": "Wataru Fujimoto"
    },
    {
      "name": "Atsushi Kurabayashi"
    },
    {
      "name": "Yusuke Okadome",
      "orcid": "0009-0003-1330-7546"
    },
    {
      "name": "Daisuke Torigoe"
    },
    {
      "name": "Tomohiko Wakayama"
    },
    {
      "name": "Haruki Horiguchi"
    },
    {
      "name": "Ryoko Kusaba"
    },
    {
      "name": "Xu Peiwen"
    },
    {
      "name": "Burçe Ergel Gurbuzbalaban"
    },
    {
      "name": "Ginger Rakestraw"
    },
    {
      "name": "Aaron Yamniuk"
    },
    {
      "name": "Gordon Teg Pipes"
    },
    {
      "name": "Leonard Adam",
      "orcid": "0000-0001-7387-7071"
    },
    {
      "name": "Keishi Miyata",
      "orcid": "0000-0003-0336-1859"
    },
    {
      "name": "Takanori Yamaguchi"
    },
    {
      "name": "Hiromasa Otake"
    },
    {
      "name": "Tohru Minamino",
      "orcid": "0000-0003-1627-6151"
    },
    {
      "name": "Seitaro Nomura",
      "orcid": "0000-0002-2957-2016"
    },
    {
      "name": "Kimitoshi Nakamura"
    },
    {
      "name": "Koichi Node",
      "orcid": "0000-0002-2534-0939"
    },
    {
      "name": "Yuichi Oike",
      "orcid": "0000-0003-3245-5395"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/14e4p3v2hqsj0.bib",
  "cited_by": 0,
  "doi": "10.1038/s41467-026-78375-2",
  "fulltext_url": null,
  "id": "14e4p3v2hqsj0",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://www.nature.com/articles/s41467-026-78375-2",
  "language": null,
  "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": [
    [
      "openalex",
      "2705|Cardiac Fibrosis and Remodeling"
    ]
  ],
  "openalex": "W7222722835",
  "pdf_url": "https://www.nature.com/articles/s41467-026-78375-2_reference.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-16",
  "publisher": "Springer Science and Business Media LLC",
  "ris": "https://research.draconitic.com/paper/14e4p3v2hqsj0.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:38Z",
      "native_id": "10.1038/s41467-026-78375-2",
      "source": "crossref",
      "url": "https://www.nature.com/articles/s41467-026-78375-2"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2705|Cardiac Fibrosis and Remodeling",
      "subfield": "cardiovascular"
    }
  ],
  "title": "Hypertensive stress rewires macrophage signaling in heart failure with preserved ejection fraction independent of obesity",
  "title_text": "Hypertensive stress rewires macrophage signaling in heart failure with preserved ejection fraction independent of obesity",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:38Z",
  "url": "https://research.draconitic.com/paper/14e4p3v2hqsj0",
  "venue": "Nature Communications",
  "versions": []
}