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Lipoprotein distribution and serum concentrations of 7alpha-hydroxy-4-cholesten-3-one and bile acids: Effects of monogenic disturbances in high density lipoprotein metabolism.
MedLine Citation:
PMID:  22010943     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Bile acid (BA) formation is considered as an important final step in reverse cholesterol transport (RCT) and high density lipoproteins (HDL) have been reported to transport BAs. We therefore investigated the effects of monogenic disturbances in human HDL metabolism on serum concentrations and lipoprotein distributions of the major 15 BA species and their precursor 7alpha-hydroxy-4-cholesten-3-one (C4). In normolipidemic plasma, about 84%, 11% and 5% of BAs were recovered in the lipoprotein depleted serum (LPDS), HDL, and the combined LDL/VLDL fraction, respectively. Conjugated BA's were slightly over-represented in HDL. For C4 the respective percentages read 23%, 21%, and 56% (41% in LDL, 15% in VLDL), respectively. Compared to unaffected family members, neither HDL cholesterol decreasing mutations in the genes encoding for apolipoprotein A-I, ATP binding cassette transporter A1, or lecithin-cholesterol acyltransferase nor HDL cholesterol increasing mutations in the genes encoding for cholesteryl ester transfer protein, or hepatic lipase were associated with significantly different serum concentrations of BA and C4. Plasma concentrations of conjugated and secondary BA's differed between heterozygous carriers of scavenger receptor BI (SCARB1) mutations and unaffected individuals (p <0.05) but this difference was not significant after correction for multiple testing. Moreover , no differences in the lipoprotein distribution of bile acids in LPDS and HDL fractions from SCARB1 heterozygotes were observed. In conclusion, despite significant recoveries of BAs and C4 in HDL and despite the metabolic relationships between RCT and BA formation, monogenic disorders of HDL metabolism do not lead to altered serum concentrations of BAs and C4.
Authors:
Carine Steiner; Adriaan G Holleboom; Ratna Karuna; Mohammad M Motazacker; Jan Albert Kuivenhoven; Ruth Frikke-Schmidt; Anne Tybjaerg-Hansen; Lucia Rohrer; Katharina M Rentsch; Arnold von Eckardstein
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-10-20
Journal Detail:
Title:  Clinical science (London, England : 1979)     Volume:  -     ISSN:  1470-8736     ISO Abbreviation:  -     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7905731     Medline TA:  Clin Sci (Lond)     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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