The thyroid receptor modulator KB3495 reduces atherosclerosis independently of total cholesterol in the circulation in ApoE deficient mice

PloS One
Lisa-Mari MörkPaolo Parini


Thyroid 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. Using 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. KB3495 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 ...Continue Reading


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Aug 17, 2014·Trends in Endocrinology and Metabolism : TEM·Rohit A SinhaPaul M Yen
Feb 18, 2016·Current Atherosclerosis Reports·L P B ElbersB Sjouke
Apr 1, 2017·International Journal of Molecular Sciences·Fabrizio DamianoLuisa Siculella
Jan 11, 2016·Acta Physiologica·D GnocchiP Parini

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