Monocyte/macrophage expression of ABCA1 has minimal contribution to plasma HDL levels
Mehrdad Haghpassand, Patricia-Ann K. Bourassa, Omar L. Francone, Robert J. Aiello
Mehrdad Haghpassand, Patricia-Ann K. Bourassa, Omar L. Francone, Robert J. Aiello
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Article

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.

Authors

Mehrdad Haghpassand, Patricia-Ann K. Bourassa, Omar L. Francone, Robert J. Aiello

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Figure 1

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PCR amplification of ABCA1 gene from WT and ABC1–/– peritoneal macrophag...
PCR amplification of ABCA1 gene from WT and ABC1–/– peritoneal macrophages. Elicited peritoneal macrophages were obtained from irradiated mice transplanted with donor bone marrow (donor bone marrow→recipient mice). Total DNA was isolated and subjected to PCR amplification using specific primers for WT ABCA1 (a) or the disrupted ABCA1 (b) gene. RNase protection assay for ABCA1 and cyclophilin was performed on 10 μg total RNA obtained from the liver and spleen of recipient mice (c). Protected ABCA1 fragments were visualized by autoradiography and quantitated by a phosphorimager. Similar levels of cyclophilin were seen in all samples.