Ezetimibe, a Potent Cholesterol Absorption Inhibitor, Inhibits the Development of Atherosclerosis in ApoE Knockout Mice
| Autor: | Harry R. Davis, Glen Tetzloff, Lizbeth M. Hoos, Douglas S Compton |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Male
Apolipoprotein E medicine.medical_specialty Arteriosclerosis medicine.drug_class Lipoproteins Cholesterol VLDL Administration Oral Aorta Thoracic Lesion Mice chemistry.chemical_compound Apolipoproteins E High-density lipoprotein Ezetimibe Internal medicine medicine Animals Cholesterol absorption inhibitor Aorta Abdominal Diet Fat-Restricted Mice Knockout Cholesterol Anticholesteremic Agents Cholesterol HDL Mice Mutant Strains Mice Inbred C57BL Endocrinology Intestinal Absorption Liver chemistry Low-density lipoprotein Disease Progression Azetidines lipids (amino acids peptides and proteins) medicine.symptom Cardiology and Cardiovascular Medicine Lipoprotein medicine.drug |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 21:2032-2038 |
| ISSN: | 1524-4636 1079-5642 |
| Popis: | Ezetimibe (SCH58235) is a potent, selective, cholesterol absorption inhibitor. The objective of this study was to determine whether ezetimibe reduces plasma cholesterol and inhibits atherogenesis in apolipoprotein E knockout (apoE−/−) mice. Cholesterol absorption was inhibited by >90% at doses of ezetimibe >3 mg/kg in apoE−/− mice. Atherosclerosis and lipoprotein changes were determined in apoE−/− mice fed a high-fat (0.15% cholesterol) “western” diet, a low-fat (0.15% cholesterol) diet, or a semisynthetic cholesterol-free diet with or without ezetimibe (5 mg/kg per day) for 6 months. Ezetimibe reduced plasma cholesterol levels from 964 to 374 mg/dL, from 726 to 231 mg/dL, and from 516 to 178 mg/dL in the western, low-fat, and cholesterol-free diet groups, respectively. The reductions occurred in the very low density and low density lipoprotein fractions, whereas high density lipoprotein cholesterol levels were increased by ezetimibe treatment. Ezetimibe reduced aortic atherosclerotic lesion surface area from 20.2% to 4.1% in the western diet group and from 24.1% to 7.0% in the low-fat cholesterol diet group. Ezetimibe reduced carotid artery atherosclerotic lesion cross-sectional area by 97% in the western and low-fat cholesterol groups and by 91% in the cholesterol-free group. Ezetimibe inhibits cholesterol absorption, reduces plasma cholesterol, increases high density lipoprotein levels, and inhibits the progression of atherosclerosis under western, low-fat, and cholesterol-free dietary conditions in apoE−/− mice. Although apoE−/− mice are more hypercholesterolemic than are humans and low density lipoprotein reductions with ezetimibe are not as pronounced clinically, ezetimibe may inhibit atherogenesis in individuals consuming restricted-fat or western diets. |
| Databáze: | OpenAIRE |
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