{
  "abstract": "Background: Cardiometabolic diseases frequently involve concurrent cardiovascular and hepatic dysfunction, yet the conserved molecular mechanisms underlying these systemic responses remain poorly defined. Objectives: To identify conserved molecular responses across complementary manifestations of cardiometabolic stress and determine whether integrated multi-organ analyses reveal therapeutically actionable targets for heart failure. Methods: Cardiac functional phenotyping, hepatic injury profiling, and bulk RNA sequencing were performed across three complementary mouse models representing distinct manifestations of cardiometabolic stress: high-fat diet plus L-NAME (HFD+LN)-induced heart failure with preserved ejection fraction (HFpEF; cardiovascular disease), Western diet (WD)-induced obesity (systemic metabolic stress), and choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD)-induced steatotic liver disease (hepatic metabolic stress). Comparative transcriptomic analyses distinguished organ-specific responses from conserved molecular signatures. Results: Each model produced distinct systemic, hepatic, and cardiac phenotypes accompanied by divergent transcriptional responses within individual organs. Cross-model and cross-organ integration identified a limited set of conserved molecular responses to cardiometabolic stress, with Serpine1, encoding plasminogen activator inhibitor-1 (PAI-1), emerging as a highly conserved candidate that exhibited preferential induction in the heart. Pharmacologic inhibition of PAI-1 significantly improved cardiac function and attenuated adverse remodeling in established HFpEF, whereas hepatic pathology was comparatively less affected, indicating differential organ-specific dependence on this pathway. Conclusions: Integrated analyses across complementary manifestations of cardiometabolic stress identified conserved molecular signatures that transcend individual disease models and organs. These findings establish a comparative framework for discovering cardiovascular therapeutic targets and identify PAI-1 as a promising mediator of cardiac remodeling in cardiometabolic disease.",
  "abstract_shown": true,
  "affiliations": [
    "University of Texas Health Science Center at Houston"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "name": "M. Saeed"
    },
    {
      "name": "H.-J. Jung"
    },
    {
      "name": "B. R. Lee"
    },
    {
      "name": "S. Patil"
    },
    {
      "name": "R. Sarkar"
    },
    {
      "name": "C. Lantz"
    },
    {
      "name": "M. J. Heo"
    },
    {
      "name": "A. Serrato"
    },
    {
      "name": "Y. A. An"
    },
    {
      "name": "K. H. Kim"
    },
    {
      "affs": [
        0
      ],
      "name": "M. DeBerge"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cg0x5rcn2xqn9.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.08.28.747839",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.08.28.747839v1.full",
  "id": "cg0x5rcn2xqn9",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.08.28.747839v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "systems biology"
    ],
    [
      "openalex",
      "2705|Cardiac Fibrosis and Remodeling"
    ]
  ],
  "openalex": "W7204804677",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.08.28.747839v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-08-28",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/cg0x5rcn2xqn9.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:27Z",
      "native_id": "10.64898/2026.08.28.747839",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.08.28.747839v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:systems biology",
      "subfield": "systems-synthetic"
    }
  ],
  "title": "Complementary Models of Cardiometabolic Stress Reveal Conserved Molecular Programs Driving Cardiac Remodeling",
  "title_text": "Complementary Models of Cardiometabolic Stress Reveal Conserved Molecular Programs Driving Cardiac Remodeling",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:27Z",
  "url": "https://research.draconitic.com/paper/cg0x5rcn2xqn9",
  "venue": "bioRxiv",
  "versions": []
}