Enhanced ABCG1 expression increases atherosclerosis in LDLr-KO mice on a western diet.
Document Type
Article
Publication Date
2006
Keywords
Animals, Aorta, Atherosclerosis, Biological-Transport, Chemokine-CCL2, Cholesterol, Cholesterol-HDL, Diet-Atherogenic, Lipids, Lipoproteins, Liver, Macrophages-Peritoneal, Mice, Mice-Transgenic, RNA-Messenger, Receptors-LDL, Tumor-Necrosis-Factor-alpha
First Page
398
Last Page
404
JAX Source
Biochem Biophys Res Commun 2006 Dec; 351(2):398-404.
Abstract
ABCG1 promotes cholesterol efflux from cells, but ABCG1(-/-) bone marrow transplant into ApoE(-/-) and LDLr(-/-) mice reduces atherosclerosis. To further investigate the role of ABCG1 in atherosclerosis, ABCG1 transgenic mice were crossed with LDLr-KO mice and placed on a high-fat western diet. Increased expression of ABCG1 mRNA was detected in liver (1.8-fold) and macrophages (2.7-fold), and cholesterol efflux from macrophages to HDL was also increased (1.4-fold) in ABCG1xLDLr-KO vs. LDLr-KO mice. No major differences were observed in total plasma lipids. However, cholesterol in the IDL-LDL size range was increased by approximately 50% in ABCG1xLDLr-KO mice compared to LDLr-KO mice. Atherosclerosis increased by 39% (10.1+/-0.8 vs 6.1+/-0.9% lesion area, p=0.02), as measured by en face analysis, and by 53% (221+/-98 vs 104+/-58x10(3)microm(2), p =0.01), as measured by cross-sectional analysis in ABCG1xLDLr-KO mice. Plasma levels for MCP-1 (1.5-fold) and TNF-alpha (1.2-fold) were also increased in ABCG1xLDLr-KO mice. In summary, these findings suggest that enhanced expression of ABCG1 increases atherosclerosis in LDLr-KO mice, despite its role in promoting cholesterol efflux from cells.
Recommended Citation
Basso F,
Amar MJ,
Wagner EM,
Vaisman B,
Paigen B,
Santamarina FS,
Remaley AT.
Enhanced ABCG1 expression increases atherosclerosis in LDLr-KO mice on a western diet. Biochem Biophys Res Commun 2006 Dec; 351(2):398-404.