The thyromimetic T-0681 protects from atherosclerosis

Abstract

This report describes studies in hyperlipidemic New Zealand White (NZW) rabbits investigating the impact of the liver-selective thyromimetic T-0681 on lipoprotein metabolism and the development of atherosclerosis. Prolonged treatment with T-0681 increased the hepatic expression of both LDL receptor and scavenger receptor class B, type I without affecting cholesteryl ester transfer protein activity. Upregulation of hepatic lipoprotein receptors was accompanied by a marked decrease of apolipoprotein B-containing lipoproteins, reflected by a 60% reduction of plasma cholesterol and a .70% reduction of plasma triglyceride levels. Most importantly, T-0681 reduced the development of atherosclerosis by 80% in NZW rabbits on high-cholesterol chow. Our data suggest that liver-selective thyromimetics, such as T-0681, may prove to be useful therapeutic agents against the development of atherosclerosis in humans.-Tancevski, I., A. Wehinger, E. Demetz, J. Hoefer, P.

Lipid lowering with thyroid hormone and thyromimetics

“…In agreement with this reasoning, evidence of reduced atherosclerosis in animal models such as cholesterolfed rabbits [20 ] and apoE-knockout mice [19 ] has now been reported using the liver-selective thyromimetic T-0681.…”

Nuclear Receptors and Their Selective Pharmacologic Modulators

“…The liver selective TR agonist T-0681, sodium;3-[4-[3-[(4-fluorophenyl)-hydroxymethyl]-4-hydroxyphenoxy]-3,5-dimethylanilino]-3-oxopropanoate (also known as KAT-681), has recently been demonstrated to have beneficial effects on atherosclerotic lesions in cholesterolfed rabbits and mice deficient in apolipoprotein E Tancevski et al, 2009). T-0681 induced the LDL and HDL receptors in rodents and in addition was found to significantly increase fecal excretion of macrophage-derived neutral and acidic sterols (Tancevski et al, 2010).…”

The Liver-Selective Thyromimetic T-0681 Influences Reverse Cholesterol Transport and Atherosclerosis Development in Mice

“…Recently, it has been shown that liver-selective thyromimetics upregulate hepatic SR-BI, which is an important component in reverse cholesterol transport (RCT) [7], [10]. By their dual action on LDL metabolism and RCT, thyromimetics could be expected to counteract atherosclerosis.…”