Monocyte/macrophage expression of ABCA1 has minimal contribution to plasmaHDL levels

Excess accumulation of cholesterol in macrophages results in foam cell prod uction and lesion development. Recent studies have demonstrated that ATP-bi nding cassette protein A1 (ABCA1) is highly regulated in macrophages and me diates the efflux of cholesterol and phospholipids to apolipoproteins, a pr ocess 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 inact ivation of ABCA1 in macrophages by bone marrow transplantation in ABCA1-def icient (ABC1(-/-)) and wild-type (WT) mice. At all times, the level of HDL in ABC1(-/-) recipient mice remained low relative to WT recipient mice irre spective of the genotype of the donor macrophage ABCA1 or high-fat feeding. Expression of WT macrophage ABCA1 in ABC1(-/-) mice resulted in a small bu t significant increase in apoA-I levels starting 2 weeks after transplantat ion. No further increase in apoAI was observed up to 14 weeks after transpl antation. The increase in apoAI was accompanied by a small but significant increase in HDL cholesterol 6 weeks after transplantation. The HDL formed a s a consequence of the expression of WT macrophage ABCA1 migrated to the al pha position in a two-dimensional gel electrophoresis. These results demons trate that monocyte/macrophage ABCA1 contributes to HDL formation; however, the contribution to the overall plasma HDL levels is minimal.