Abstract 1721: Deletion of Both Macrophage ABCG1 and ApoE Independently Promotes Atherosclerotic Lesion Development in LDL Receptor Knockout Mice
Objective ATP-binding cassette transporter G1 (ABCG1) and apolipoprotein E (apoE) play a role in macrophage cholesterol efflux and consequently the development of atherosclerosis. Although a possible interaction between ABCG1 and apoE in cholesterol efflux was postulated, the combined action of these proteins in atherosclerosis is still unclear.
Methods and Results LDL receptor knockout (KO) mice were transplanted with bone marrow from ABCG1/apoE double KO (dKO) mice, their respective single knockouts, and wild-type (WT) controls. After feeding a high-fat/high-cholesterol diet for 6 weeks, no differences were found in serum lipid levels. However, the mean atherosclerotic lesion area in dKO transplanted animals (187 ± 18 × 103 μ m2) was 1.4-fold (p < 0.01) increased compared to single knockouts (ABCG1 KO: 138 ± 5 × 103 μm2; apoE KO: 131 ± 7 × 103 μm2) and 1.9-fold (p< 0.001) as compared to WT controls (97 ± 15 × 103 μm2). In vitro cholesterol efflux experiments confirmed that combined deletion of ABCG1 and apoE resulted in a larger attenuation of macrophage cholesterol efflux to HDL as compared to single knockouts.
Conclusions Deletion of macrophage ABCG1 or apoE does lead to a moderate increase in atherosclerotic lesion development while combined deletion of ABCG1 and apoE induces a more dramatic increase in atherosclerosis. These results indicate an added, independent effect for both macrophage ABCG1 and apoE in atherosclerosis.