2026-10-12T10:32:42Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33987226 2026-09-24T17:23:34Z category_4 category_7 category_13 category_16 category_19 category_873 category_46 category_734 category_132 category_134 portal_5 item_type_3 month_year_09_2026

<p>Raw data for all quantitative analyses.</p> Xuedong Bai (1455343) Wenjie Fei (3365780) Jingzhou Fang (6691439) Chaomin Kong (25104913) Yaqi Xiang (25104916) Yuele Tian (25104919) Limin Wei (6691448) Biochemistry Medicine Genetics Physiology Pharmacology Chemical Sciences not elsewhere classified Immunology Biological Sciences not elsewhere classified Infectious Diseases Virology warranting mechanistic validation pressing clinical need performed across disease nlrp3 inflammasome signaling direct pathway perturbation density lipoprotein cholesterol suppressed aortic nlrp3 eight weeks (< xlink "> atherosclerosis aortic plaque morphology nlrp3 inflammatory phenotype corrected atherogenic dyslipidemia total p65 ratio improving lipid metabolism 1 &# 946 resmetirom attenuates atherosclerosis resmetirom attenuated atherosclerosis suppressed interleukin 8 weeks 1 expression &# 954 alleviate atherosclerosis plaque burden inflammatory pathways inflammatory cytokines associated dyslipidemia way anova vascular inflammation vascular anti translational potential thyroid hormone staining compared serum lipids response regression oxidative stress oil red n </ model controls macrophage polarization interacting lipid findings support fat diet exploratory cross dependent manner data support <div> <p>Background</p><p>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.</p> <p>Methods</p><p>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 (<i>n</i> = 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.</p> <p>Results</p><p>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.</p> <p>Conclusions</p><p>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.</p></div> 2026-09-24T17:23:25Z Dataset Dataset 10.1371/journal.pone.0359161.s007 https://figshare.com/articles/dataset/_p_Raw_data_for_all_quantitative_analyses_p_/33987226 CC BY 4.0