| Ritonavir protects against the development of atherosclerosis in APOE*3-Leiden mice. | |
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MedLine Citation:
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PMID: 20060117 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: The use of the HIV-protease inhibitor ritonavir (RTV) is associated with induction of hypertriglyceridemia, which is a cardiovascular risk factor. Therefore, we investigated the effect of RTV on atherosclerosis development in APOE*3-Leiden transgenic mice, a model for human-like lipoprotein metabolism and atherosclerosis. METHODS AND RESULTS: APOE*3-Leiden mice were fed a Western-type diet without or with RTV (35 mg/kg/day) for 19 weeks. RTV increased plasma TG levels throughout the study (approximately 2-fold; P<0.05). Despite these increased TG levels, RTV decreased the atherosclerotic lesion area in the aortic root (-57%; P<0.05), concomitant with reduced macrophage area (-72%; P<0.01) and decreased lesion severity. This could not be explained by reduced inflammatory markers in plasma (i.e. serum amyloid A, E-selectin and fibrinogen), nor by decreased lipid accumulation in macrophages or increased cholesterol efflux from macrophages, as assessed using peritoneal macrophages in vitro. Rather, whereas RTV did not affect plasma total cholesterol levels, RTV decreased (V)LDL-cholesterol and increased cholesterol in apoE-rich large HDL. CONCLUSION: Despite inducing hypertriglyceridemia, RTV decreases atherosclerotic lesion area and severity, associated with decreased (V)LDL-cholesterol and increased atheroprotective apoE-rich large HDL. |
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Authors:
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Marion A M den Boer; Marit Westerterp; Jitske de Vries-van der Weij; Yanan Wang; Lihui Hu; Sonia M S Espirito Santo; Teake Kooistra; Peter Reiss; Johannes A Romijn; Louis M Havekes; Patrick C N Rensen |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-12-01 |
Journal Detail:
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Title: Atherosclerosis Volume: 210 ISSN: 1879-1484 ISO Abbreviation: Atherosclerosis Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-05-31 Completed Date: 2010-12-06 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0242543 Medline TA: Atherosclerosis Country: Ireland |
Other Details:
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Languages: eng Pagination: 381-7 Citation Subset: IM |
Copyright Information:
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Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved. |
Affiliation:
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Department of General Internal Medicine, Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, Netherlands. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apolipoprotein E3 / genetics* Apolipoproteins E / genetics* Atherosclerosis / drug therapy* Cholesterol / chemistry Female HIV Protease Inhibitors / pharmacology Hypertriglyceridemia / drug therapy Lipids / chemistry Macrophages / metabolism Macrophages, Peritoneal / metabolism Mice Mice, Transgenic Risk Factors Ritonavir / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Apolipoprotein E3; 0/Apolipoproteins E; 0/HIV Protease Inhibitors; 0/Lipids; 0/Ritonavir; 0/apolipoprotein E3 (Leidein); 57-88-5/Cholesterol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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