Increased atherosclerosis in mice reconstituted with apolipoprotein E null macrophages.
Macrophage-derived foam cells express apolipoprotein E (apoE) abundantly in atherosclerotic lesions. To examine the physiologic role of apoE secretion by the macrophage in atherogenesis, bone marrow transplantation was used to reconstitute C57BL/6 mice with macrophages that were either null or wild type for the apoE gene. After 13 weeks on an atherogenic diet, C57BL/6 mice reconstituted with apoE null marrow developed 10-fold more atherosclerosis than controls in the absence of significant differences in serum cholesterol levels or lipoprotein profiles. ApoE expression was absent in the macrophage-derived foam cells of C57BL/6 mice reconstituted with apoE null marrow. Thus, lack of apoE expression by the macrophage promotes foam cell formation. These data support a protective role for apoE expression by the macrophage in early atherogenesis.
Fazio
S
S
Department of Medicine, Vanderbilt University, Nashville, TN 37232, USA. sergio.fazio@mcmail.vanderbilt.edu
Babaev
V R
VR
Murray
A B
AB
Hasty
A H
AH
Carter
K J
KJ
Gleaves
L A
LA
Atkinson
J B
JB
Linton
M F
MF
D000818:Animals; D001011:Aorta / Q000473:pathology; D001057:Apolipoproteins E / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D001161:Arteriosclerosis / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D002784:Cholesterol / Q000097:blood; D004036:Diet, Atherogenic; D005260:Female; D008074:Lipoproteins / Q000097:blood; D008264:Macrophages / Q000378:metabolism* / Q000637:transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains
D001057:Apolipoproteins E; D008074:Lipoproteins; D002784:Cholesterol