| Increased appearance rate of 27-hydroxycholesterol in vivo in hypercholesterolemia: A possible compensatory mechanism. | |
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MedLine Citation:
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PMID: 21546230 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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BACKGROUND AND AIMS: The first step in the alternative pathway of bile acid biosynthesis is the 27-hydroxylation of cholesterol, which takes place both in liver and extrahepatic tissues. This pathway is believed to play a role in peripheral cholesterol degradation. Aim of this study was to investigate the impact of hyperlipidemia on 27-hydroxycholesterol appearance rate, and to assess the effects induced by treatment with statins. METHODS AND RESULTS: Seven patients with familial hypercholesterolemia and eight patients with familial combined hyperlipidemia underwent determination of 27-hydroxylation rates in vivo by i.v. infusion of deuterated 27-hydroxycholesterol. Isotope enrichment was assayed by gas chromatography-mass spectrometry, allowing to calculate 27-hydroxycholesterol appearance rates. Six normocholesterolemic subjects were regarded as controls. In some hypercholesterolemic patients the infusions were repeated during treatment with atorvastatin or rosuvastatin. Hydroxylation rates were higher in hypercholesterolemic patients (8.7 ± 2.5 mg/h; controls, 3.4 ± 2.0 mg/h; combined hyperlipidemia, 4.4 ± 1.6 mg/h; mean ± SD, P < 0.01 vs both). After statin treatment, both plasma cholesterol levels and hydroxylation rates dropped by nearly 50%. No difference was detectable between the two statins. A linear correlation was shown between plasma cholesterol and 27-hydroxylation rates. CONCLUSION: Hypercholesterolemia associates with increased 27-hydroxycholesterol appearance rates, which decrease during hypocholesterolemic treatment. The correlation with cholesterol levels supports the view that 27-hydroxylation may act as a compensatory mechanism in a condition of larger plasma cholesterol pool. A regulatory role for hepatic and extrahepatic nuclear receptors seems reasonable. These data prompt novel pharmacological approaches for the management of hypercholesterolemia and the prevention of atherosclerosis. |
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Authors:
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M Bertolotti; M Del Puppo; F Corna; C Anzivino; C Gabbi; E Baldelli; L Carulli; P Loria; M Galli Kienle; N Carulli |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-5-3 |
Journal Detail:
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Title: Nutrition, metabolism, and cardiovascular diseases : NMCD Volume: - ISSN: 1590-3729 ISO Abbreviation: - Publication Date: 2011 May |
Date Detail:
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Created Date: 2011-5-6 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9111474 Medline TA: Nutr Metab Cardiovasc Dis Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 Elsevier B.V. All rights reserved. |
Affiliation:
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Dipartimento di Medicina, Endocrinologia, Metabolismo e Geriatria, Università degli Studi di Modena e Reggio Emilia, Nuovo Ospedale Civile, via Giardini 1355, 41100 Modena, Italy. |
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