{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T18:06:17Z","timestamp":1790273177501,"version":"4.1.0"},"reference-count":38,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hebei Province Medical Science Research Project Plan","award":["20250296"],"award-info":[{"award-number":["20250296"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats: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 \u03b2 (THR-\u03b2) agonists can alleviate atherosclerosis while avoiding the cardiotoxic adverse effects associated with thyroid hormone. Resmetirom is an oral, once-daily, liver-targeted selective THR-\u03b2 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Apolipoprotein E-deficient (ApoE\n                      <jats:sup>-<\/jats:sup>\n                      \/\n                      <jats:sup>-<\/jats:sup>\n                      ) 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                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200910 per group). Serum lipids, inflammatory cytokines, aortic plaque morphology, NLRP3 inflammasome signaling, NF-\u03baB 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats: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-1\u03b2 (IL-1\u03b2) by 59.28%; Western blotting showed lower p-p65\/total p65 ratio and higher I\u03baB\u03b1\/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-\u03baB\/ROS\/macrophage readouts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Resmetirom attenuated atherosclerosis-associated dyslipidemia, plaque burden and vascular inflammation in HFD ApoE\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice. The data support an association between resmetirom treatment and suppression of the NF-\u03baB\/ROS-NLRP3 inflammatory phenotype, warranting mechanistic validation in models with direct pathway perturbation. These findings support its translational potential in atherosclerotic cardiovascular disease.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0359161","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:23:16Z","timestamp":1790270596000},"page":"e0359161","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Resmetirom attenuates atherosclerosis-associated dyslipidemia and vascular inflammation in high-fat diet-fed ApoE\u2212\/\u2212 mice"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6268-7262","authenticated-orcid":true,"given":"Xuedong","family":"Bai","sequence":"first","affiliation":[{"name":"Hebei Medical University","place":["Shijiazhuang, Hebei, China"],"department":["Department of Internal Medicine"]},{"name":"Hebei General Hospital","place":["Shijiazhuang, Hebei, 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China"],"department":["Department of Geriatric Cardiology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqi","family":"Xiang","sequence":"additional","affiliation":[{"name":"Hebei Medical University","place":["Shijiazhuang, Hebei, China"],"department":["Department of Internal Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuele","family":"Tian","sequence":"additional","affiliation":[{"name":"Hebei Medical University","place":["Shijiazhuang, Hebei, China"],"department":["Department of Internal Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Limin","family":"Wei","sequence":"additional","affiliation":[{"name":"Hebei Medical University","place":["Shijiazhuang, Hebei, China"],"department":["Department of Internal Medicine"]},{"name":"Hebei General Hospital","place":["Shijiazhuang, Hebei, China"],"department":["Department of 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