title: 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.
authors.affiliation: Department of Internal Medicine, Innsbruck Medical University, Innsbruck, Austria. ivan.tancevski@i-med.ac.at
authors.forename: Ivan
authors.initials: I
authors.lastname: Tancevski
authors.forename: Andreas
authors.initials: A
authors.lastname: Wehinger
authors.forename: Egon
authors.initials: E
authors.lastname: Demetz
authors.forename: Julia
authors.initials: J
authors.lastname: Hoefer
authors.forename: Philipp
authors.initials: P
authors.lastname: Eller
authors.forename: Eva
authors.initials: E
authors.lastname: Huber
authors.forename: Ursula
authors.initials: U
authors.lastname: Stanzl
authors.forename: Kristina
authors.initials: K
authors.lastname: Duwensee
authors.forename: Kristina
authors.initials: K
authors.lastname: Auer
authors.forename: Wilfried
authors.initials: W
authors.lastname: Schgoer
authors.forename: Volker
authors.initials: V
authors.lastname: Kuhn
authors.forename: Catherine
authors.initials: C
authors.lastname: Fievet
authors.forename: Frans
authors.initials: F
authors.lastname: Stellaard
authors.forename: Mats
authors.initials: M
authors.lastname: Rudling
authors.forename: Bernhard
authors.initials: B
authors.lastname: Foeger
authors.forename: Josef R
authors.initials: JR
authors.lastname: Patsch
authors.forename: Andreas
authors.initials: A
authors.lastname: Ritsch
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001011:Aorta / Q000033:anatomy & histology / Q000473:pathology; D050197:Atherosclerosis / Q000517:prevention & control*; D018955:CD36 Antigens / Q000378:metabolism; D002460:Cell Line; D002791:Cholesterol, Dietary; D004032:Diet; D004195:Disease Models, Animal; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008314:Malonates / Q000627:therapeutic use*; D010647:Phenyl Ethers / Q000627:therapeutic use*; D011817:Rabbits
chemical_list: D000924:Anticholesteremic Agents; D018955:CD36 Antigens; D002791:Cholesterol, Dietary; D008314:Malonates; C496199:N-(4-(3-((4-fluorophenyl)hydroxymethyl)-4-hydroxyphenoxy)-3,5-dimethylphenyl) malonamic acid sodium; D010647:Phenyl Ethers