Beschreibung:
<jats:p>Cholesterol efflux from macrophage foam cells to HDL or its apolipoproteins is thought to have an important anti‐atherogenic role. Two major ABC transporters are involved in this process: ABCA1 which promotes cholesterol efflux to lipid‐poor apolipoproteins, and ABCG1 which promotes cholesterol efflux to HDL particles. While bone marrow transplantation studies have indicated an anti‐atherogenic role of macrophage ABCA1, results with ABCG1 deficient bone marrow have been mixed. We reported a decrease in atherosclerosis in LDLR−/− mice transplanted with ABCG1−/− bone marrow. This unexpected result appeared related to compensatory up‐regulation of ABCA1 and apoE secretion in ABCG1−/− macrophages. To assess this hypothesis we recently transplanted double KO ABCA1−/−ABCG1−/− bone marrow into LDLr deficient mice, resulting in a dramatic increase in atherosclerosis compared to WT or single KO BM recipients. This indicates overlapping roles and mutual compensation of ABCA1 and ABCG1 in macrophage cholesterol efflux and athero‐protection. However, ABCG1 appears to have a specific role in protecting macrophages from apoptosis induced by oxidized LDL, related to the ability of ABCG1 (but not ABCA1) to promote efflux of specific oxysterols such as 7‐ketocholesterol from macrophages to HDL. Large HDL that accumulates in CETP deficiency is enriched in apoE and LCAT and is highly efficient at promoting macrophage sterol efflux via the ABCG1 pathway. It is interesting to speculate that HDL/ABCG1 could reverse oxysterol‐mediated macrophage apoptosis and inflammatory gene expression in atherosclerotic lesions. In addition, ABCG1 is high expressed in endothelial cells suggesing a possible role of HDL/ABCG1 in maintenance of endothelial function.</jats:p>