Total body ABCG1 expression protects against early atherosclerotic lesion development in mice.
OBJECTIVE
ABCG1 has recently been identified as a facilitator of cholesterol and phospholipid efflux from macrophages to HDL. In bone marrow transplantation studies, we and others have now shown that the absence of macrophage ABCG1 may differentially influence atherosclerotic lesions dependent on the experimental setting and/or the stage of atherosclerotic lesion development. To further define the role of ABCG1 in atherogenesis, we investigated in the current study the effect of total body deficiency of ABCG1 on atherosclerotic lesion development.


RESULTS
ABCG1-/- mice and wild-type littermates were fed an atherogenic diet for 12 weeks to induce atherosclerotic lesion formation. Both before and after the start of the atherogenic diet, serum lipid levels and lipoprotein profiles did not differ significantly between the two groups. In addition no significant difference in serum apoE levels was found after diet feeding. In wild-type mice the atherogenic diet induced the formation of macrophage-rich early lesions (size: 24+/-7x10(3) microm2 [n=6]). Feeding ABCG1-/- mice the atherogenic diet led to a significant 1.9-fold stimulation of atherosclerotic lesion size (46+/-6x10(3) microm2 [n=7]; Student t test P=0.034 and Mann-Whitney test P=0.050) compared with controls, suggesting a clear antiatherogenic role for ABCG1. At the same time, excessive lipid accumulation was observed in macrophage-rich areas of the lungs and spleens of ABCG1-/- mice as compared with wild-type mice.


CONCLUSIONS
Total body ABCG1 expression protects against early atherosclerotic lesion development.
Out
Ruud
R
Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, Einsteinweg 55, 2333CC Leiden, The Netherlands. r.out@lacdr.leidenuniv.nl
Hoekstra
Menno
M
Meurs
Illiana
I
de Vos
Paula
P
Kuiper
Johan
J
Van Eck
Miranda
M
Van Berkel
Theo J C
TJ
D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001057:Apolipoproteins E / Q000032:analysis / Q000378:metabolism*; D050197:Atherosclerosis / Q000503:physiopathology / Q000517:prevention & control*; D015153:Blotting, Western; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006706:Homeostasis; D050356:Lipid Metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011336:Probability; D012016:Reference Values; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric
C419353:ABCG1 protein, human; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D001057:Apolipoproteins E