Document Detail

Monocyte/macrophage expression of ABCA1 has minimal contribution to plasma HDL levels.
MedLine Citation:
PMID:  11696576     Owner:  NLM     Status:  MEDLINE    
Excess accumulation of cholesterol in macrophages results in foam cell production and lesion development. Recent studies have demonstrated that ATP-binding cassette protein A1 (ABCA1) is highly regulated in macrophages and mediates the efflux of cholesterol and phospholipids to apolipoproteins, a process necessary for HDL formation. The goal of this study was to determine the contribution of monocyte/macrophage ABCA1 to HDL formation in vivo. We generated mice expressing ABCA1 in macrophages and mice with selected inactivation of ABCA1 in macrophages by bone marrow transplantation in ABCA1-deficient (ABC1(-/-)) and wild-type (WT) mice. At all times, the level of HDL in ABC1(-/-) recipient mice remained low relative to WT recipient mice irrespective of the genotype of the donor macrophage ABCA1 or high-fat feeding. Expression of WT macrophage ABCA1 in ABC1(-/-) mice resulted in a small but significant increase in apoA-I levels starting 2 weeks after transplantation. No further increase in apoAI was observed up to 14 weeks after transplantation. The increase in apoAI was accompanied by a small but significant increase in HDL cholesterol 6 weeks after transplantation. The HDL formed as a consequence of the expression of WT macrophage ABCA1 migrated to the alpha position in a two-dimensional gel electrophoresis. These results demonstrate that monocyte/macrophage ABCA1 contributes to HDL formation; however, the contribution to the overall plasma HDL levels is minimal.
M Haghpassand; P A Bourassa; O L Francone; R J Aiello
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  108     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2001 Nov 
Date Detail:
Created Date:  2001-11-06     Completed Date:  2001-12-07     Revised Date:  2013-04-18    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1315-20     Citation Subset:  AIM; IM    
Pfizer Global Research and Development, Groton, Connecticut 06340, USA.
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MeSH Terms
ATP-Binding Cassette Transporters / biosynthesis*,  genetics
Bone Marrow Transplantation
Crosses, Genetic
Electrophoresis, Gel, Two-Dimensional
Lipoproteins, HDL / blood*
Macrophages / metabolism*
Macrophages, Peritoneal / metabolism
Monocytes / metabolism*
Protein Binding
Tangier Disease
Time Factors
Reg. No./Substance:
0/ATP binding cassette transporter 1; 0/Lipoproteins, HDL
Comment In:
J Clin Invest. 2001 Nov;108(9):1273-5   [PMID:  11696569 ]

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