The thyromimetic T-0681 protects from atherosclerosis

Ivan Tancevski, Andreas Wehinger, Egon Demetz, Julia Hoefer, Philipp Eller, Eva Huber, Ursula Stanzl, Kristina Duwensee, Kristina Auer, Wilfried Schgoer, Volker Kuhn, Catherine Fievet, Frans Stellaard, Mats Rudling, Bernhard Foeger, Josef R. Patsch, and Andreas Ritsch

Dpt. of Internal Medicine, Innsbruck Medical University, Innsbruck 6020

Corresponding Author: ivan.tancevski{at}i-med.ac.at

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-BI, without affecting cholesteryl ester transfer protein activity. Upregulation of hepatic lipoprotein receptors was accompanied by a marked decrease of apoB-containing lipoproteins, reflected by a 60% reduction of plasma cholesterol and a more than 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 useful therapeutic agents against the development of atherosclerosis in humans.

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