Dataset Information

Monocyte/macrophage expression of ABCA1 has minimal contribution to plasma HDL levels.

ABSTRACT: 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.

SUBMITTER: Haghpassand M

PROVIDER: S-EPMC209438 | biostudies-literature | 2001 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Monocyte/macrophage expression of ABCA1 has minimal contribution to plasma HDL levels.

Haghpassand M M Bourassa P A PA Francone O L OL Aiello R J RJ

The Journal of clinical investigation 20011101 9

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 ...[more]

PMID: 11696576

Similar Datasets

Project description:BACKGROUND:Studies on the associations of the adenosine triphosphate-binding cassette transporter A1 gene (ABCA1) rs2230806, rs2230808, and rs2066714 polymorphisms with plasma lipid levels have reported apparently conflicting findings. This meta-analysis aimed to clarify the relationships between the 3 polymorphisms and fasting lipid levels. METHODS:A comprehensive search of the literature was carried out by using the databases including Medline, Google Scholar, Web of Science, Embase, Cochrane Library, CNKI, Wanfang, and VIP. The studies that presented mean lipids and standard deviations or standard errors according to the rs2230806, rs2230808, and/or rs2066714 genotypes were examined and included. The random effects model was used. Standardized mean difference and 95% confidence interval were used to assess the differences in lipid levels between the genotypes. Heterogeneity among studies was tested by Cochran's ?-based Q-statistic, and Galbraith plots were used to detect the potential sources of heterogeneity. Publication bias was assessed by Begg's rank correlation test as well as funnel plots. RESULTS:Sixty-two studies (48,452 subjects), 12 studies (9853 subjects) and 14 studies (10,727 subjects) were identified for the rs2230806, rs2230808, and rs2066714 polymorphisms, respectively. A dominant model was used for all the polymorphisms in this meta-analysis. The A allele carriers of the rs2230806 polymorphism had higher levels of high-density lipoprotein cholesterol (HDL-C) (P?<.001), and lower levels of low-density lipoprotein cholesterol (LDL-C) (P?=.03) and triglycerides (TG) (P?<.01) than the non-carriers. The A allele carriers of the rs2230808 polymorphism had higher levels of total cholesterol (TC) (P?<.001) than the non-carriers. The G allele carriers of the rs2066714 polymorphism had higher levels of TC (P?<.01) and HDL-C (P?=?.02) than the non-carriers. CONCLUSION:The ABCA1 rs2230806, rs2230808, and rs2066714 polymorphisms are significantly associated with plasma lipid levels in the present meta-analysis.

Dataset Information

Monocyte/macrophage expression of ABCA1 has minimal contribution to plasma HDL levels.

Publications

Monocyte/macrophage expression of ABCA1 has minimal contribution to plasma HDL levels.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets