| Circulating proprotein convertase subtilisin kexin type 9 has a diurnal rhythm synchronous with cholesterol synthesis and is reduced by fasting in humans. | |
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MedLine Citation:
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PMID: 20884874 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: To gain insight into the function of proprotein convertase subtilisin kexin type 9 (PCSK9) in humans by establishing whether circulating levels are influenced by diurnal, dietary, and hormonal changes. METHODS AND RESULTS: We monitored circulating PCSK9 in a set of dynamic human experiments and could show that serum PCSK9 levels display a diurnal rhythm that closely parallels that of cholesterol synthesis, measured as serum lathosterol. In contrast to these marked diurnal changes in cholesterol metabolism, serum low-density lipoprotein (LDL) cholesterol levels remained stable during the diurnal cycle. Depletion of liver cholesterol by treatment with the bile acid-binding resin, cholestyramine, abolished the diurnal rhythms of both PCSK9 and lathosterol. Fasting (>18 hours) strongly reduced circulating PCSK9 and lathosterol levels, whereas serum LDL levels remained unchanged. Growth hormone, known to be increased during fasting in humans, reduced circulating PCSK9 in parallel to LDL cholesterol levels. CONCLUSIONS: Throughout the day, and in response to fasting and cholesterol depletion, circulating PCSK9 displays marked variation, presumably related to oscillations in hepatic cholesterol that modify its activity in parallel with cholesterol synthesis. In addition to this sterol-mediated regulation, additional effects on LDL receptors may be mediated by hormones directly influencing PCSK9. |
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Authors:
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Lena Persson; Guoqing Cao; Lars Ståhle; Beatrice G Sjöberg; Jason S Troutt; Robert J Konrad; Cecilia Gälman; Håkan Wallén; Mats Eriksson; Ingiäld Hafström; Suzanne Lind; Maria Dahlin; Per Amark; Bo Angelin; Mats Rudling |
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Publication Detail:
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Type: Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't Date: 2010-09-30 |
Journal Detail:
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Title: Arteriosclerosis, thrombosis, and vascular biology Volume: 30 ISSN: 1524-4636 ISO Abbreviation: Arterioscler. Thromb. Vasc. Biol. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-18 Completed Date: 2010-12-21 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9505803 Medline TA: Arterioscler Thromb Vasc Biol Country: United States |
Other Details:
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Languages: eng Pagination: 2666-72 Citation Subset: IM |
Affiliation:
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Department of Endocrinology, Center for Biosciences and Nutrition, Karolinska Institutet at Karolinska University Hospital, Huddinge, Stockholm, Sweden. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Anticholesteremic Agents
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administration & dosage Cholesterol / biosynthesis*, blood Cholesterol, LDL / blood Cholestyramine Resin / administration & dosage Circadian Rhythm* Cross-Over Studies Down-Regulation Energy Intake Fasting / blood* Female Heptanoic Acids / administration & dosage Human Growth Hormone / administration & dosage Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage Ketogenic Diet Liver / drug effects, metabolism Male Pyrroles / administration & dosage Receptors, LDL / metabolism Serine Endopeptidases / blood* Sweden |
| Chemical | |
Reg. No./Substance:
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0/Anticholesteremic Agents; 0/Cholesterol, LDL; 0/Heptanoic Acids; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 0/Pyrroles; 0/Receptors, LDL; 11041-12-6/Cholestyramine Resin; 110862-48-1/atorvastatin; 12629-01-5/Human Growth Hormone; 57-88-5/Cholesterol; 80-99-9/lathosterol; EC 3.4.21.-/PCSK9 protein, human; EC 3.4.21.-/Serine Endopeptidases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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