ArticlePloS one2013
The thyroid receptor modulator KB3495 reduces atherosclerosis independently of total cholesterol in the circulation in ApoE deficient mice.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 7 citations in OpenAlex.
- Resmetirom attenuates atherosclerosis-associated dyslipidemia and vascular inflammation in high-fat diet-fed ApoE-/- mice.PloS one · 2026Article
- Deciphering thyroid function and CIMT: a Mendelian randomization study of the U-shaped influence mediated by apolipoproteins.Frontiers in endocrinology · 2024Article
- Action of Thyroid Hormones, T3 and T2, on Hepatic Fatty Acids: Differences in Metabolic Effects and Molecular Mechanisms.International journal of molecular sciences · 2017Review
- Thyroid Hormone Mimetics: the Past, Current Status and Future Challenges.Current atherosclerosis reports · 2016Review
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThyroid hormones (TH) regulate cholesterol metabolism but their use as lipid-lowering drugs is restricted due to negative cardiac effects. TH mimetic compounds modulating TH receptor β (THRβ) have been designed as potential drugs, reducing serum cholesterol levels while avoiding apparent deleterious cardiac effects.
objectiveUsing ApoE deficient mice, we examined whether KB3495, a TH mimetic compound, reduces atherosclerosis and if there is a synergistic effect with atorvastatin. The effect of KB3495 was investigated after 10 and 25 weeks.
resultsKB3495 treatment reduced atherosclerotic plaque formation in aorta and decreased the cholesteryl ester (CE) content by 57%. Treatment with KB3495 was also associated with a reduction of macrophage content in the atherosclerotic plaques and reduced serum levels of IL-1β, TNFalpha, IL-6, Interferon γ, MCP-1 and M-CSF. Serum lipoprotein analysis showed no change in total cholesterol levels in ApoB-containing lipoproteins. KB3495 alone increased fecal BA excretion by 90%. The excretion of neutral sterols increased in all groups, with the largest increase in the combination group (350%). After 25 weeks, the animals treated with KB3495 showed 50% lower CE levels in the skin and even further reductions were observed in the combination group where the CE levels were reduced by almost 95% as compared to controls.
conclusionKB3495 treatment reduced atherosclerosis independently of total cholesterol levels in ApoB-containing lipoproteins likely by stimulation of sterol excretion from the body and by inhibition of the inflammatory response.
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