Effect of macrophage-derived apolipoprotein E on established atherosclerosis in apolipoprotein E-deficient mice.
Apolipoprotein E-deficient (apoE(-/-)) mice have hyperlipidemia and develop spontaneous atherosclerosis in a time-dependent manner. Although macrophage-derived apoE has been shown to prevent the development of atherosclerosis in apoE(-/-) mice, whether it would induce regression of established atherosclerosis is unknown. To determine this, 8-week-old apoE(-/-) mice were transplanted with apoE(+/+) bone marrow. Four weeks after transplantation, when plasma cholesterol levels had reached normal levels, a group of mice (n=12) were killed and their aortic lesions were measured and used as a baseline to judge regression. Twelve and 20 weeks after transplantation, aortic lesion areas of the mice were 9340+/-2184 micrometer(2) (mean+/-SEM, n=8) and 12 211+/-1433 micrometer(2) (n=9), respectively, values not significantly different from the lesion areas of the baseline mice (12 347+/-2487 micrometer(2); n=12, P>0.05). In contrast, apoE(-/-) mice reconstituted with apoE(-/-) bone marrow developed severe atherosclerotic lesions (453 036+/-29 767 micrometer(2), n=7) 20 weeks after transplantation. These data suggest that macrophage-derived apoE was insufficient to induce significant regression of established atherosclerotic lesions in apoE(-/-) mice, although it was sufficient to eliminate hypercholesterolemia and prevent progression of aortic lesions.
Shi
W
W
Department of Medicine, School of Medicine, University of California, Los Angeles, USA.
Wang
X
X
Wang
N J
NJ
McBride
W H
WH
Lusis
A J
AJ
D000818:Animals; D001011:Aorta / Q000473:pathology; D001057:Apolipoproteins E / Q000032:analysis / Q000172:deficiency* / Q000235:genetics; D001161:Arteriosclerosis / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D016026:Bone Marrow Transplantation; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D006949:Hyperlipidemias / Q000097:blood / Q000235:genetics*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013997:Time Factors; D017211:Treatment Failure; D014280:Triglycerides / Q000097:blood
D001057:Apolipoproteins E; D008078:Cholesterol, LDL; D014280:Triglycerides; D002784:Cholesterol