{
  "abstract": "Background: Activation of the renin-angiotensin system (RAS) contributes to aortic diseases caused by fibrillin-1 haploinsufficiency (Fbn1C1041G/+). However, whether RAS activation influences mitral valve disease associated with FBN1 variants remains undefined. This study determined whether inhibition or augmentation of the RAS affects mitral valve pathology in Fbn1C1041G/+ mice. Methods: Angiotensinogen (AGT) antisense oligonucleotides (ASOs) were administered for 12 weeks to inhibit the RAS in male and female Fbn1C1041G/+ mice. To augment the RAS, mice were infused with angiotensin II (AngII; 1,000 ng/kg/min) for 28 days. Mitral valve and heart function were monitored by ultrasound. At termination, hearts were dissected free and tissue sectioned to assess mitral valve leaflet thickness and pathology. Results: Mitral valve leaflet thickness was significantly increased in Fbn1C1041G/+ mice compared to Fbn1+/+ littermates of both sexes. ASO-mediated AGT inhibition did not alter this phenotype despite markedly reduced plasma AGT concentrations. AngII infusion increased mitral valve leaflet thickness in Fbn1C1041G/+ mice with increased proteoglycan and collagen content, while exerting minimal effects in Fbn1+/+ mice. Twenty-five percent of AngII-infused Fbn1C1041G/+ mice died of non-vascular causes. Ultrasound showed mitral valve dysfunction in AngII-infused Fbn1C1041G/+ mice. Grossly expanded left atria were common in AngII-infused Fbn1C1041G/+ mice. These markedly enlarged left atria contained increased fibrosis, macrophage accumulation, and platelet-rich masses. Conclusions: Mitral valves of Fbn1C1041G/+ mice did not respond to AGT inhibition but were markedly more susceptible to AngII infusion, with greater increases in thickness and compositional changes than mitral valves of Fbn1+/+ mice. In addition, AngII promoted mitral valve dysfunction that were associated with pronounced left atrial pathology.",
  "abstract_shown": true,
  "affiliations": [
    "University of Kentucky"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "name": "M. K. Franklin"
    },
    {
      "name": "D. A. Howatt"
    },
    {
      "name": "A. C. Pettey"
    },
    {
      "name": "J. J. Moorleghen"
    },
    {
      "name": "B. M. Levitan"
    },
    {
      "name": "A. E. Mullick"
    },
    {
      "name": "J. Saffitz"
    },
    {
      "name": "H. S. Lu"
    },
    {
      "affs": [
        0
      ],
      "name": "A. Daugherty"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e7a7qpzdy2wz7.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.02.755732",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.02.755732v1.full",
  "id": "e7a7qpzdy2wz7",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.02.755732v1",
  "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",
      "pharmacology and toxicology"
    ],
    [
      "openalex",
      "1311|Connective tissue disorders research"
    ]
  ],
  "openalex": "W7221140212",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.02.755732v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-02",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/e7a7qpzdy2wz7.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:26:43Z",
      "native_id": "10.64898/2026.10.02.755732",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.02.755732v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:pharmacology and toxicology",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Angiotensin II Promotes Mitral Valve and Left Atrial Pathology in Fibrillin-1C1041G/+ Mice",
  "title_text": "Angiotensin II Promotes Mitral Valve and Left Atrial Pathology in Fibrillin-1C1041G/+ Mice",
  "type": "preprint",
  "updated_at": "2026-10-30T12:26:43Z",
  "url": "https://research.draconitic.com/paper/e7a7qpzdy2wz7",
  "venue": "bioRxiv",
  "versions": []
}