{
  "abstract": "Introduction: Hypothyroidism (HT) is clinically associated with an increased risk of cardiovascular disease, yet the shared molecular mechanisms underlying subclinical atherosclerosis (sAS) in hypothyroid patients remain poorly understood. This study aims to identify common transcriptomic signatures and regulatory axes between these two conditions.\n\nMethods: We performed an integrated transcriptomic analysis of peripheral whole-blood datasets retrieved from the Gene Expression Omnibus (GSE176153 and GSE221615). To minimize sex-based biological bias, the analysis was restricted to female samples. Differential expression, functional enrichment, network topology, and transcription factor prediction were performed to identify shared differentially expressed genes (SDEGs) and candidate transcriptional regulators. The classification performance of selected pivotal SDEGs and predicted transcription factors was assessed by receiver operating characteristic (ROC) analysis. Public transcriptomic data from myeloid-specific Tshr-knockout murine macrophages (GSE275079) were additionally examined to explore the myeloid context of TSH–TSHR signaling, followed by in vitro RT-qPCR validation in human THP-1 macrophages exposed to TSH and LPS.\n\nResults: We identified 20 female-restricted SDEGs enriched in pathways related to B-cell proliferation and activation. Integration of functional enrichment, functional network analysis, and PPI topology highlighted six pivotal genes: BLK, CD19, CD180, TNFRSF13C, SPIB, and FCRLA. SPI1 and MEF2A were identified as key candidate regulators collectively targeting this gene set. Exploratory ROC analyses showed discriminatory capacity for several pivotal SDEGs and candidate transcription factors across the study cohorts, with some of these findings also observed in an external cohort of advanced atherosclerotic disease. Analysis of Tshr-knockout murine macrophage data revealed enrichment in lymphocyte and mononuclear cell proliferation pathways, alongside downregulation of Ifrd1. In human THP-1 macrophages, TSH alone and in combination with LPS were associated with a significant downregulation of IFRD1 expression.\n\nDiscussion: These findings suggest a potential sex-specific immune-endocrine link between thyroid dysfunction and atherosclerotic disease, characterized by a shared transcriptomic axis converging on B-cell-associated pivotal genes and candidate transcriptional regulators. Exploratory myeloid analyses further identified TSH-associated downregulation of IFRD1.",
  "abstract_shown": true,
  "affiliations": [
    "Centro de Investigaciones Endocrinológicas “Dr. César Bergadá”, Consejo Nacional de Investigaciones Científicas y Técnicas - Fundación de Endocrinología Infantil - División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Emiliana María Torres"
    },
    {
      "affs": [
        0
      ],
      "name": "Diego Alejandro Raffo"
    },
    {
      "affs": [
        0
      ],
      "name": "Mariana Lorena Tellechea"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dmgaq95w6hnsw.bib",
  "cited_by": 0,
  "doi": "10.3389/fbinf.2026.1932220",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13731356/",
  "id": "dmgaq95w6hnsw",
  "issns": [
    "2673-7647"
  ],
  "landing_url": "https://doi.org/10.3389/fbinf.2026.1932220",
  "language": "en",
  "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": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "2712|Thyroid Disorders and Treatments"
    ]
  ],
  "openalex": "W7223150789",
  "pdf_url": "https://www.frontiersin.org/journals/bioinformatics/articles/10.3389/fbinf.2026.1932220/pdf",
  "pmcid": "PMC13731356",
  "pmid": "42985003",
  "published": "2026-10-21",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/dmgaq95w6hnsw.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:21:34Z",
      "native_id": "PMC13731356",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fbinf.2026.1932220"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2712|Thyroid Disorders and Treatments",
      "subfield": "endocrinology-metabolism"
    }
  ],
  "title": "A whole-blood transcriptomic analysis of shared molecular mechanisms between subclinical atherosclerosis and hypothyroidism in women",
  "title_text": "A whole-blood transcriptomic analysis of shared molecular mechanisms between subclinical atherosclerosis and hypothyroidism in women",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:21:34Z",
  "url": "https://research.draconitic.com/paper/dmgaq95w6hnsw",
  "venue": "Frontiers in Bioinformatics",
  "versions": []
}