Journal of Lipid Research (May 2009)
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,
- Andreas Ritsch
Affiliations
- Ivan Tancevski
- Department of Internal Medicine, Innsbruck Medical University, Innsbruck, Austria; Department of Surgery, Innsbruck Medical University, Innsbruck, Austria; Department of Internal Medicine, Landeskrankenhaus Bregenz, Bregenz, Austria; Département d’Athérosclérose, Institut Pasteur de Lille, Lille Cedex, France; Laboratory of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University Medical Center Groningen, Groningen, The Netherlands; Department for Endocrinology, Metabolism, and Diabetes, Molecular Nutrition Unit, and Departments of Medicine and Biosciences and Nutrition, Karolinska Institutet, Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden
- Andreas Wehinger
- Department of Internal Medicine, Innsbruck Medical University, Innsbruck, Austria; Department of Surgery, Innsbruck Medical University, Innsbruck, Austria; Department of Internal Medicine, Landeskrankenhaus Bregenz, Bregenz, Austria; Département d’Athérosclérose, Institut Pasteur de Lille, Lille Cedex, France; Laboratory of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University Medical Center Groningen, Groningen, The Netherlands; Department for Endocrinology, Metabolism, and Diabetes, Molecular Nutrition Unit, and Departments of Medicine and Biosciences and Nutrition, Karolinska Institutet, Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden
- Egon Demetz
- Department of Internal Medicine, Innsbruck Medical University, Innsbruck, Austria; Department of Surgery, Innsbruck Medical University, Innsbruck, Austria; Department of Internal Medicine, Landeskrankenhaus Bregenz, Bregenz, Austria; Département d’Athérosclérose, Institut Pasteur de Lille, Lille Cedex, France; Laboratory of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University Medical Center Groningen, Groningen, The Netherlands; Department for Endocrinology, Metabolism, and Diabetes, Molecular Nutrition Unit, and Departments of Medicine and Biosciences and Nutrition, Karolinska Institutet, Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden
- Julia Hoefer
- Department of Internal Medicine, Innsbruck Medical University, Innsbruck, Austria; Department of Surgery, Innsbruck Medical University, Innsbruck, Austria; Department of Internal Medicine, Landeskrankenhaus Bregenz, Bregenz, Austria; Département d’Athérosclérose, Institut Pasteur de Lille, Lille Cedex, France; Laboratory of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University Medical Center Groningen, Groningen, The Netherlands; Department for Endocrinology, Metabolism, and Diabetes, Molecular Nutrition Unit, and Departments of Medicine and Biosciences and Nutrition, Karolinska Institutet, Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden
- Philipp Eller
- Department of Internal Medicine, Innsbruck Medical University, Innsbruck, Austria; Department of Surgery, Innsbruck Medical University, Innsbruck, Austria; Department of Internal Medicine, Landeskrankenhaus Bregenz, Bregenz, Austria; Département d’Athérosclérose, Institut Pasteur de Lille, Lille Cedex, France; Laboratory of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University Medical Center Groningen, Groningen, The Netherlands; Department for Endocrinology, Metabolism, and Diabetes, Molecular Nutrition Unit, and Departments of Medicine and Biosciences and Nutrition, Karolinska Institutet, Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden
- Eva Huber
- Department of Internal Medicine, Innsbruck Medical University, Innsbruck, Austria; Department of Surgery, Innsbruck Medical University, Innsbruck, Austria; Department of Internal Medicine, Landeskrankenhaus Bregenz, Bregenz, Austria; Département d’Athérosclérose, Institut Pasteur de Lille, Lille Cedex, France; Laboratory of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University Medical Center Groningen, Groningen, The Netherlands; Department for Endocrinology, Metabolism, and Diabetes, Molecular Nutrition Unit, and Departments of Medicine and Biosciences and Nutrition, Karolinska Institutet, Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden
- Ursula Stanzl
- Department of Internal Medicine, Innsbruck Medical University, Innsbruck, Austria; Department of Surgery, Innsbruck Medical University, Innsbruck, Austria; Department of Internal Medicine, Landeskrankenhaus Bregenz, Bregenz, Austria; Département d’Athérosclérose, Institut Pasteur de Lille, Lille Cedex, France; Laboratory of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University Medical Center Groningen, Groningen, The Netherlands; Department for Endocrinology, Metabolism, and Diabetes, Molecular Nutrition Unit, and Departments of Medicine and Biosciences and Nutrition, Karolinska Institutet, Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden
- Kristina Duwensee
- Department of Internal Medicine, Innsbruck Medical University, Innsbruck, Austria; Department of Surgery, Innsbruck Medical University, Innsbruck, Austria; Department of Internal Medicine, Landeskrankenhaus Bregenz, Bregenz, Austria; Département d’Athérosclérose, Institut Pasteur de Lille, Lille Cedex, France; Laboratory of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University Medical Center Groningen, Groningen, The Netherlands; Department for Endocrinology, Metabolism, and Diabetes, Molecular Nutrition Unit, and Departments of Medicine and Biosciences and Nutrition, Karolinska Institutet, Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden
- Kristina Auer
- Department of Internal Medicine, Innsbruck Medical University, Innsbruck, Austria; Department of Surgery, Innsbruck Medical University, Innsbruck, Austria; Department of Internal Medicine, Landeskrankenhaus Bregenz, Bregenz, Austria; Département d’Athérosclérose, Institut Pasteur de Lille, Lille Cedex, France; Laboratory of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University Medical Center Groningen, Groningen, The Netherlands; Department for Endocrinology, Metabolism, and Diabetes, Molecular Nutrition Unit, and Departments of Medicine and Biosciences and Nutrition, Karolinska Institutet, Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden
- Wilfried Schgoer
- Department of Internal Medicine, Innsbruck Medical University, Innsbruck, Austria; Department of Surgery, Innsbruck Medical University, Innsbruck, Austria; Department of Internal Medicine, Landeskrankenhaus Bregenz, Bregenz, Austria; Département d’Athérosclérose, Institut Pasteur de Lille, Lille Cedex, France; Laboratory of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University Medical Center Groningen, Groningen, The Netherlands; Department for Endocrinology, Metabolism, and Diabetes, Molecular Nutrition Unit, and Departments of Medicine and Biosciences and Nutrition, Karolinska Institutet, Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden
- Volker Kuhn
- Department of Internal Medicine, Innsbruck Medical University, Innsbruck, Austria; Department of Surgery, Innsbruck Medical University, Innsbruck, Austria; Department of Internal Medicine, Landeskrankenhaus Bregenz, Bregenz, Austria; Département d’Athérosclérose, Institut Pasteur de Lille, Lille Cedex, France; Laboratory of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University Medical Center Groningen, Groningen, The Netherlands; Department for Endocrinology, Metabolism, and Diabetes, Molecular Nutrition Unit, and Departments of Medicine and Biosciences and Nutrition, Karolinska Institutet, Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden
- Catherine Fievet
- Department of Internal Medicine, Innsbruck Medical University, Innsbruck, Austria; Department of Surgery, Innsbruck Medical University, Innsbruck, Austria; Department of Internal Medicine, Landeskrankenhaus Bregenz, Bregenz, Austria; Département d’Athérosclérose, Institut Pasteur de Lille, Lille Cedex, France; Laboratory of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University Medical Center Groningen, Groningen, The Netherlands; Department for Endocrinology, Metabolism, and Diabetes, Molecular Nutrition Unit, and Departments of Medicine and Biosciences and Nutrition, Karolinska Institutet, Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden
- Frans Stellaard
- Department of Internal Medicine, Innsbruck Medical University, Innsbruck, Austria; Department of Surgery, Innsbruck Medical University, Innsbruck, Austria; Department of Internal Medicine, Landeskrankenhaus Bregenz, Bregenz, Austria; Département d’Athérosclérose, Institut Pasteur de Lille, Lille Cedex, France; Laboratory of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University Medical Center Groningen, Groningen, The Netherlands; Department for Endocrinology, Metabolism, and Diabetes, Molecular Nutrition Unit, and Departments of Medicine and Biosciences and Nutrition, Karolinska Institutet, Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden
- Mats Rudling
- Department of Internal Medicine, Innsbruck Medical University, Innsbruck, Austria; Department of Surgery, Innsbruck Medical University, Innsbruck, Austria; Department of Internal Medicine, Landeskrankenhaus Bregenz, Bregenz, Austria; Département d’Athérosclérose, Institut Pasteur de Lille, Lille Cedex, France; Laboratory of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University Medical Center Groningen, Groningen, The Netherlands; Department for Endocrinology, Metabolism, and Diabetes, Molecular Nutrition Unit, and Departments of Medicine and Biosciences and Nutrition, Karolinska Institutet, Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden
- Bernhard Foeger
- Department of Internal Medicine, Innsbruck Medical University, Innsbruck, Austria; Department of Surgery, Innsbruck Medical University, Innsbruck, Austria; Department of Internal Medicine, Landeskrankenhaus Bregenz, Bregenz, Austria; Département d’Athérosclérose, Institut Pasteur de Lille, Lille Cedex, France; Laboratory of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University Medical Center Groningen, Groningen, The Netherlands; Department for Endocrinology, Metabolism, and Diabetes, Molecular Nutrition Unit, and Departments of Medicine and Biosciences and Nutrition, Karolinska Institutet, Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden
- Josef R. Patsch
- Department of Internal Medicine, Innsbruck Medical University, Innsbruck, Austria; Department of Surgery, Innsbruck Medical University, Innsbruck, Austria; Department of Internal Medicine, Landeskrankenhaus Bregenz, Bregenz, Austria; Département d’Athérosclérose, Institut Pasteur de Lille, Lille Cedex, France; Laboratory of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University Medical Center Groningen, Groningen, The Netherlands; Department for Endocrinology, Metabolism, and Diabetes, Molecular Nutrition Unit, and Departments of Medicine and Biosciences and Nutrition, Karolinska Institutet, Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden
- Andreas Ritsch
- Department of Internal Medicine, Innsbruck Medical University, Innsbruck, Austria; Department of Surgery, Innsbruck Medical University, Innsbruck, Austria; Department of Internal Medicine, Landeskrankenhaus Bregenz, Bregenz, Austria; Département d’Athérosclérose, Institut Pasteur de Lille, Lille Cedex, France; Laboratory of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University Medical Center Groningen, Groningen, The Netherlands; Department for Endocrinology, Metabolism, and Diabetes, Molecular Nutrition Unit, and Departments of Medicine and Biosciences and Nutrition, Karolinska Institutet, Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden
- Journal volume & issue
-
Vol. 50,
no. 5
pp. 938 – 944
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.
