Increased atherosclerosis in mice with vascular ATP-binding cassette transporter G1 deficiency--brief report.
OBJECTIVE
The objective of this study was to investigate the role of vascular ATP-binding cassette transporter G1 (ABCG1) in atherogenesis without a confounding difference in macrophage ABCG1 expression. ABCG1 is highly expressed in macrophages and endothelial cells. ABCG1 preserves endothelial function by maintaining endothelial NO synthase activity and by reducing adhesion molecule expression and monocyte adhesion.


RESULTS
To investigate the role of vascular ABCG1 in atherosclerosis in vivo Abcg1(-/-)/Ldlr(-/-) and Ldlr(-/-) mice were transplanted with wild-type bone marrow and fed a Western-type diet for 12 or 23 weeks. The atherosclerotic lesion area was similar in both groups after 12 weeks but was increased in Abcg1(-/-)/Ldlr(-/-) recipients after 23 weeks, especially in the aortic arch (2.2-fold; P<0.01). Endothelial NO synthase-mediated vascular relaxation was impaired in male Abcg1(-/-)/Ldlr(-/-) recipients.


CONCLUSIONS
Our data show an atheroprotective role of vascular ABCG1, especially in the aortic arch, likely related to its role in the preservation of endothelial NO synthase activity.
Westerterp
Marit
M
Division of Molecular Medicine, Department of Medicine, Columbia University, New York, NY 10032, USA.
Koetsveld
Joris
J
Yu
Shuiqing
S
Han
Seongah
S
Li
Rong
R
Goldberg
Ira J
IJ
Welch
Carrie L
CL
Tall
Alan R
AR
D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000503:physiopathology; D050197:Atherosclerosis / Q000378:metabolism*; D004195:Disease Models, Animal; D008074:Lipoproteins / Q000172:deficiency* / Q000378:metabolism; D051379:Mice
C487540:ABCG1 protein, mouse; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D008074:Lipoproteins