| Cellular phospholipid and cholesterol efflux in high-density lipoprotein deficiency. | |
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MedLine Citation:
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PMID: 12642355 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Prospective studies have examined the relationship between coronary artery disease and low plasma levels of high-density lipoprotein cholesterol (HDL-C). METHODS AND RESULTS: We investigated the causes of hypoalphalipoproteinemia (HypoA; HDL-C <5th percentile) in 64 subjects (12 women and 52 men). Apolipoprotein AI-mediated cellular cholesterol and phospholipid efflux were measured in fibroblasts from HypoA subjects, 9 controls, 2 patients with Tangier disease, and 5 patients with hyperalphalipoproteinemia. A phospholipid efflux defect was defined as <70% of controls. Mean HDL-C was 0.49+/-0.21 mmol/L. Cholesterol and phospholipid efflux correlated strongly (r=0.72, P<0.001). Phospholipid efflux and HDL-C (r=0.64, P<0.001) correlated in HypoA subjects. However, phospholipid or cholesterol efflux was no longer a determinant of HDL-C levels at higher levels (> approximately 1.0 mmol/L) of HDL-C. In HypoA subjects, 4 cases of Tangier disease and 6 of familial HDL deficiency (heterozygous Tangier disease) were identified (10 of 64; 16%). In the remaining 54 subjects, mean lipid efflux was not significantly different from controls and subjects with hyperalphalipoproteinemia. A phospholipid efflux defect was identified in 7 additional HypoA subjects, and a cholesterol efflux defect was detected in 11 subjects. In 2 of these subjects, the ABCA1 gene was ruled out as the cause of the efflux defect, while in 3, the low HDL-C trait segregated with the ABCA1 gene locus. CONCLUSIONS: Lipidation of lipid-poor apolipoprotein AI may not be a major determinant of cholesterol accumulation within more mature HDL particles and increasing cholesterol or phospholipid efflux beyond normal levels may not lead to increase in plasma HDL-C levels. ABCA1 is essential in the initial steps of HDL formation but other plasma events are major modulators of HDL-C levels. |
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Authors:
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Michel Marcil; Rachel Bissonnette; Jérôme Vincent; Larbi Krimbou; Jacques Genest |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Circulation Volume: 107 ISSN: 1524-4539 ISO Abbreviation: Circulation Publication Date: 2003 Mar |
Date Detail:
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Created Date: 2003-03-18 Completed Date: 2003-04-10 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0147763 Medline TA: Circulation Country: United States |
Other Details:
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Languages: eng Pagination: 1366-71 Citation Subset: AIM; IM |
Affiliation:
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Department of Cardiovascular Genetics, McGill University Health Centre, Montréal, Canada. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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ATP-Binding Cassette Transporters
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genetics Adult Biological Transport Cells, Cultured Cholesterol / metabolism* Cholesterol, HDL / deficiency* Female Fibroblasts / metabolism Humans Male Middle Aged Mutation Phospholipids / metabolism* Tangier Disease / blood, genetics, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/ATP binding cassette transporter 1; 0/ATP-Binding Cassette Transporters; 0/Cholesterol, HDL; 0/Phospholipids; 57-88-5/Cholesterol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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