OBJECTIVE: ATP-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+/-18x10(3)microm(2)) was 1.4-fold (p<0.01) increased compared to single knockouts (Abcg1 KO: 138+/-5x10(3)microm(2); Apoe KO: 131+/-7x10(3)microm(2)) and 1.9-fold (p<0.001) as compared to WT controls (97+/-15x10(3)microm(2)). 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.
OBJECTIVE:ATP-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+/-18x10(3)microm(2)) was 1.4-fold (p<0.01) increased compared to single knockouts (Abcg1 KO: 138+/-5x10(3)microm(2); Apoe KO: 131+/-7x10(3)microm(2)) and 1.9-fold (p<0.001) as compared to WT controls (97+/-15x10(3)microm(2)). 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.
Authors: Bart Lammers; Ying Zhao; Menno Hoekstra; Reeni B Hildebrand; Dan Ye; Illiana Meurs; Theo J C Van Berkel; Miranda Van Eck Journal: PLoS One Date: 2011-10-11 Impact factor: 3.240
Authors: Götz Münch; Andreas Bültmann; Zhongmin Li; Hans-Peter Holthoff; Julia Ullrich; Silvia Wagner; Martin Ungerer Journal: Heart Int Date: 2012-06-25
Authors: Menno Hoekstra; Vanessa Frodermann; Tim van den Aardweg; Ronald J van der Sluis; Johan Kuiper Journal: PLoS One Date: 2013-11-12 Impact factor: 3.240