- 作者：Bart Lammers ; Ruud Out ; Reeni B. Hildebr ; Carmel M. Quinn ; David Williamson ; Menno Hoekstra ; Illiana Meurs ; Theo J.C. Van Berkel ; Wendy Jessup ; Mir ; a Van Eck
- 关键词：Abcg1 ; Apoe ; Atherosclerosis ; Macrophage ; Cholesterol ; Bone marrow transplantation
- 刊名：Atherosclerosis
- 出版年：2009
- 出版时间：August 2009
- 年：2009
- 卷：205
- 期：2
- 页码：420-426
- 全文大小：663 K
ObjectiveATP-binding cassette transporter G1 (Abcg1) and apolipoprotein E (Apoe) play a role in macrophage cholesterol efflux and consequently the development of atherosclerosis. A possible interaction between Abcg1 and Apoe in cholesterol efflux was postulated, but the potential combined action of these proteins on atherosclerotic lesion formation is unclear.Methods
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 and challenged with a high-fat/high-cholesterol diet for 6 weeks to induce atherosclerosis.
Results
No differences were found in serum lipid levels. The mean atherosclerotic lesion area in dKO transplanted animals (187 ± 18 × 103 μm2) 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 established that combined deletion of Abcg1 and Apoe leads to a larger attenuation of macrophage cholesterol efflux to HDL as compared to single knockouts.
Conclusions
Single deletion of macrophage Abcg1 or Apoe does lead to a moderate non-significant increase in atherosclerotic lesion development as tested by ANOVA, while combined deletion of Abcg1 and Apoe induces a more dramatic and significant increase in atherosclerosis. Our results indicate an additive, independent effect for both macrophage Abcg1 and Apoe in the prevention of atherosclerosis.