<p>Raw data for all quantitative analyses.</p>

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>