{
  "abstract": "Endothelial barrier failure contributes to edema, tissue hypoperfusion, and organ dysfunction during inflammatory critical illness. RhoB has emerged as a regulator of tight junction disruption in human microvascular endothelial cells, but whether clinically used drugs can modulate RhoB-dependent barrier failure remains unclear. We tested whether simvastatin preserves human dermal microvascular endothelial cell barrier function during TNF stimulation and examined the role of mevalonate-dependent RhoB localization and activation. Simvastatin pretreatment attenuated TNF-induced loss of transendothelial electrical resistance and preserved junctional ZO-1 and claudin-5 organization. Simvastatin reduced membrane-associated and increased nuclear RhoB, decreased active RhoB, and suppressed myosin light chain phosphorylation. RhoB silencing phenocopied the barrier-protective effect of simvastatin, and combined RhoB silencing and simvastatin did not provide additive protection. Mevalonate supplementation reversed simvastatin-mediated preservation of barrier function, restored peripheral RhoB localization, and restored MLC phosphorylation. These findings identify mevalonate-dependent RhoB spatial regulation as a statin-sensitive mechanism contributing to inflammatory microvascular barrier dysfunction.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pediatrics, Yale University, USA"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "name": "A. Morales-Maldonado"
    },
    {
      "name": "J. S. Pober"
    },
    {
      "affs": [
        0
      ],
      "name": "R. W. Pierce"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/c5txje13jq2xq.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.28.762609",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.28.762609v1.full",
  "id": "c5txje13jq2xq",
  "issns": [
    "2692-8205"
  ],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.28.762609v1",
  "language": "en",
  "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",
      "cell biology"
    ],
    [
      "heading",
      "Article"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.28.762609v1.full.pdf",
  "pmcid": "PMC13734092",
  "pmid": "42990546",
  "published": "2026-10-28",
  "publisher": "Cold Spring Harbor Laboratory Preprints",
  "ris": "https://research.draconitic.com/paper/c5txje13jq2xq.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:21:09Z",
      "native_id": "10.64898/2026.10.28.762609",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.28.762609v1"
    },
    {
      "first_seen": "2026-11-08T12:23:44Z",
      "native_id": "PMC13734092",
      "source": "pmc",
      "url": "https://doi.org/10.64898/2026.10.28.762609"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:cell biology",
      "subfield": "cell-biology"
    }
  ],
  "title": "Simvastatin Preserves Human Microvascular Endothelial Barrier Function Through Mevalonate-Dependent Regulation of RhoB Localization and Activation",
  "title_text": "Simvastatin Preserves Human Microvascular Endothelial Barrier Function Through Mevalonate-Dependent Regulation of RhoB Localization and Activation",
  "type": "preprint",
  "updated_at": "2026-11-08T12:23:44Z",
  "url": "https://research.draconitic.com/paper/c5txje13jq2xq",
  "venue": "bioRxiv",
  "versions": []
}