{ "abstract": "Background: Atherosclerosis is driven by interacting lipid and inflammatory pathways. There remains a pressing clinical need for drugs that exert both lipid-lowering and vascular anti-inflammatory effects. Studies have suggested that thyroid hormone receptor β (THR-β) agonists can alleviate atherosclerosis while avoiding the cardiotoxic adverse effects associated with thyroid hormone. Resmetirom is an oral, once-daily, liver-targeted selective THR-β agonist. It has attracted attention for improving lipid metabolism, yet its effects on vascular inflammatory phenotypes remain poorly clarified. We investigated the effects of resmetirom on atherosclerosis-associated dyslipidemia, plaque burden and vascular inflammatory phenotypes. Methods: Apolipoprotein E-deficient (ApoE-/-) mice fed a high-fat diet (HFD) for 8 weeks were randomized to vehicle, low-dose (3 mg/kg/day), or high-dose (10 mg/kg/day) resmetirom for eight weeks (n = 10 per group). Serum lipids, inflammatory cytokines, aortic plaque morphology, NLRP3 inflammasome signaling, NF-κB activation, oxidative stress, and macrophage polarization were analyzed by one-way ANOVA with Tukey post hoc testing; dose-response regression was performed across disease-bearing groups. Results: Resmetirom treatment reduced aortic plaque burden, corrected atherogenic dyslipidemia, and suppressed aortic NLRP3 and caspase-1 expression in a dose-dependent manner. High-dose resmetirom lowered low-density lipoprotein cholesterol (LDL-C) by 39.48%, and reduced aortic lipid accumulation on Oil Red O staining compared to model controls. Additionally, it suppressed interleukin-1β (IL-1β) by 59.28%; Western blotting showed lower p-p65/total p65 ratio and higher IκBα/GAPDH abundance. Flow-cytometric ROS intensity decreased by 35.56%, and the M1/M2 macrophage ratio decreased by 72.81%. Exploratory cross-assay analyses showed coherent associations among systemic cytokines and aortic NF-κB/ROS/macrophage readouts. Conclusions: Resmetirom attenuated atherosclerosis-associated dyslipidemia, plaque burden and vascular inflammation in HFD ApoE−/− mice. The data support an association between resmetirom treatment and suppression of the NF-κB/ROS-NLRP3 inflammatory phenotype, warranting mechanistic validation in models with direct pathway perturbation. These findings support its translational potential in atherosclerotic cardiovascular disease.", "abstract_shown": true, "affiliations": [ "Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, China", "Department of Geriatric Cardiology, Hebei General Hospital, Shijiazhuang, Hebei, China", "Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, China", "Department of Endocrinology, Langfang People’s Hospital, Langfang, Hebei, China" ], "article_type": "Research Article", "arxiv": null, "author_total": 7, "authors": [ { "affs": [ 0 ], "name": "Xuedong Bai" }, { "affs": [ 1 ], "name": "Wenjie Fei" }, { "affs": [ 2 ], "name": "Jingzhou Fang" }, { "affs": [ 3 ], "name": "Chaomin Kong" }, { "name": "Yaqi Xiang" }, { "name": "Yuele Tian" }, { "name": "Limin Wei" } ], "bibtex": "https://research.draconitic.com/paper/8tyd15b80enad.bib", "cited_by": 0, "doi": "10.1371/journal.pone.0359161", "fulltext_url": null, "id": "8tyd15b80enad", "issns": [ "1932-6203" ], "landing_url": "https://doi.org/10.1371/journal.pone.0359161", "language": null, "licence": "CC-BY-4.0", "licence_label": "CC BY 4.0", "licence_source": "journal", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "2403|Atherosclerosis and Cardiovascular Diseases" ], [ "plos", "/Biology and life sciences/Biochemistry/Lipids" ], [ "plos", "/Biology and life sciences/Biochemistry/Lipids/Oils" ], [ "plos", "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Blood cells/White blood cells/Macrophages" ], [ "plos", "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Immune cells/White blood cells/Macrophages" ], [ "plos", "/Biology and life sciences/Developmental biology/Molecular development/Cytokines" ], [ "plos", "/Biology and life sciences/Immunology/Immune cells/White blood cells/Macrophages" ], [ "plos", "/Biology and life sciences/Immunology/Immune response/Inflammation" ], [ "plos", "/Biology and life sciences/Immunology/Immune system/Innate immune system/Cytokines" ], [ "plos", "/Biology and life sciences/Physiology/Immune physiology/Cytokines" ], [ "plos", "/Medicine and health sciences/Clinical medicine/Signs and symptoms/Inflammation" ], [ "plos", "/Medicine and health sciences/Immunology/Immune cells/White blood cells/Macrophages" ], [ "plos", "/Medicine and health sciences/Immunology/Immune response/Inflammation" ], [ "plos", "/Medicine and health sciences/Immunology/Immune system/Innate immune system/Cytokines" ], [ "plos", "/Medicine and health sciences/Medical conditions/Inflammatory diseases" ], [ "plos", "/Medicine and health sciences/Medical conditions/Metabolic disorders/Dyslipidemia" ], [ "plos", "/Medicine and health sciences/Vascular medicine/Atherosclerosis" ] ], "openalex": "W7214191134", "pdf_url": "https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0359161&type=printable", "pmcid": null, "pmid": null, "published": "2026-09-24", "publisher": "Public Library of Science", "ris": "https://research.draconitic.com/paper/8tyd15b80enad.ris", "sources": [ { "first_seen": "2026-10-30T12:17:43Z", "native_id": "10.1371/journal.pone.0359161", "source": "plos", "url": "https://doi.org/10.1371/journal.pone.0359161" } ], "subjects": [ { "field": "biology", "origin": "plos:immunology", "subfield": "immunology" } ], "title": "Resmetirom attenuates atherosclerosis-associated dyslipidemia and vascular inflammation in high-fat diet-fed ApoE⁻/⁻ mice", "title_text": "Resmetirom attenuates atherosclerosis-associated dyslipidemia and vascular inflammation in high-fat diet-fed ApoE⁻/⁻ mice", "type": "peer-reviewed", "updated_at": "2026-10-30T12:17:43Z", "url": "https://research.draconitic.com/paper/8tyd15b80enad", "venue": "PLOS One", "versions": [] }