{
  "abstract": "Background: Low-density lipoprotein receptor-related protein 1 (LRP1) in smooth muscle cells (SMCs) is essential for maintaining aortic wall integrity. This study investigated whether deletion of LRP1 in SMCs induces region-specific aortic pathology and evaluated a potential therapeutic strategy. Methods: Lrp1-floxed mice were bred with Sm22-Cre+/0 mice to generate mice with SMC-LRP1 deletion (SMC-LRP1-/-) and wild-type littermates (SMC-LRP1+/+). Micro-computed tomography (micro-CT) was used to visualize the aorta, and aortic tissue sections were characterized histologically. To evaluate a potential therapeutic strategy, antisense oligonucleotides (ASOs) targeting hepatocyte-derived angiotensinogen (AGT) were administered to inhibit AGT synthesis. Results: Immunostaining and Western blotting confirmed LRP1 deletion in aortic SMCs. At 40 weeks of age, micro-CT revealed marked increases in aortic width and volume. Although dilatation occurred throughout the aorta, the infrarenal region exhibited the greatest expansion in both male and female SMC-LRP1-/- mice compared with SMC-LRP1+/+ littermates; subsequent analyses therefore focused on this region. LRP1 deletion in SMCs caused pronounced SMC loss and increased collagen deposition in the infrarenal aorta. Inhibition of hepatocyte-derived AGT with ASO attenuated infrarenal aortic dilatation and preserved aortic wall integrity in both male and female mice. Conclusions: Deletion of LRP1 in SMCs causes progressive aortic dilatation that includes the infrarenal aorta. Pharmacologic inhibition of hepatocyte-derived AGT attenuates infrarenal aortic dilatation.",
  "abstract_shown": true,
  "affiliations": [
    "University of Kentucky"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "name": "M. Franklin"
    },
    {
      "name": "G. Fan"
    },
    {
      "name": "B. Li"
    },
    {
      "name": "P. Wang"
    },
    {
      "name": "D. A. Howatt"
    },
    {
      "name": "J. Moorleghen"
    },
    {
      "name": "A. E. Mullick"
    },
    {
      "name": "A. Daugherty"
    },
    {
      "affs": [
        0
      ],
      "name": "H. S. Lu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0xn48m4hewpy8.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.16.759442",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.16.759442v1.full",
  "id": "0xn48m4hewpy8",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.16.759442v1",
  "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",
      "pathology"
    ],
    [
      "openalex",
      "2740|Aortic aneurysm repair treatments"
    ]
  ],
  "openalex": "W7223204254",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.16.759442v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-16",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/0xn48m4hewpy8.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:29:10Z",
      "native_id": "10.64898/2026.10.16.759442",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.16.759442v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:pathology",
      "subfield": "general"
    }
  ],
  "title": "Deletion of LRP1 in Smooth Muscle Cells Induces Infrarenal Aortic Aneurysms in Mice",
  "title_text": "Deletion of LRP1 in Smooth Muscle Cells Induces Infrarenal Aortic Aneurysms in Mice",
  "type": "preprint",
  "updated_at": "2026-10-30T12:29:10Z",
  "url": "https://research.draconitic.com/paper/0xn48m4hewpy8",
  "venue": "bioRxiv",
  "versions": []
}