Combined Deletion of Macrophage ABCA1 and ABCG1 Leads to Massive Lipid Accumulation in Tissue Macrophages and Distinct Atherosclerosis at Relatively Low Plasma Cholesterol Levels
- 1 February 2008
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Arteriosclerosis, Thrombosis, and Vascular Biology
- Vol. 28 (2), 258-264
- https://doi.org/10.1161/atvbaha.107.156935
Abstract
Objective— The purpose of this study was to evaluate the effect of the combined deletion of ABCA1 and ABCG1 expression in macrophages on foam cell formation and atherosclerosis. Methods and Results— LDL receptor knockout (KO) mice were transplanted with bone marrow from ABCA1/ABCG1 double KO (dKO) mice. Plasma cholesterol levels after 6 weeks of Western-type diet (WTD) feeding were significantly lower in dKO transplanted mice than ABCA1 KO, ABCG1 KO, and control transplanted animals. Extreme foam cell formation was present in macrophages of various tissues and the peritoneal cavity of dKO transplanted animals. Furthermore, severe hypoplasia of the thymus and a significant decrease in CD4-positive T cells in blood was observed. Despite relatively low plasma cholesterol levels dKO transplanted animals developed lesion sizes of 156±19×10 3 μm 2 after only 6 weeks of WTD feeding. Lesions, however, were smaller than single ABCA1 KO transplanted animals (226±30×10 3 μm 2 ; P 3 μm 2 ) and WT transplanted mice (112±15×10 3 μm 2 ). Conclusions— Macrophage ABCA1 and ABCG1 play a crucial role in the prevention of macrophage foam cell formation, whereas combined deletion only modestly influences atherosclerosis which is associated with an attenuated increase in WTD-induced plasma cholesterol and decreased proinflammatory CD4-positive T cell counts.Keywords
This publication has 28 references indexed in Scilit:
- Macrophage ABCA1 and ABCG1, but not SR-BI, promote macrophage reverse cholesterol transport in vivoJCI Insight, 2007
- Characterization of liver disease and lipid metabolism in the Niemann‐Pick C1 mouseJournal of Cellular Biochemistry, 2007
- T Cells in AtherogenesisArteriosclerosis, Thrombosis, and Vascular Biology, 2006
- Enhanced ABCG1 expression increases atherosclerosis in LDLr-KO mice on a western dietBiochemical and Biophysical Research Communications, 2006
- Macrophage ATP-Binding Cassette Transporter A1 Overexpression Inhibits Atherosclerotic Lesion Progression in Low-Density Lipoprotein Receptor Knockout MiceArteriosclerosis, Thrombosis, and Vascular Biology, 2006
- ABCA1 and ABCG1 Synergize to Mediate Cholesterol Export to ApoA-IArteriosclerosis, Thrombosis, and Vascular Biology, 2006
- Diet and Murine AtherosclerosisArteriosclerosis, Thrombosis, and Vascular Biology, 2006
- Scavenger receptors: friend or foe in atherosclerosis?Current Opinion in Lipidology, 2005
- ABCG1 has a critical role in mediating cholesterol efflux to HDL and preventing cellular lipid accumulationCell Metabolism, 2005
- Genetic Background Selectively Influences Innominate Artery AtherosclerosisArteriosclerosis, Thrombosis, and Vascular Biology, 2003