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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:2261.)
© 2000 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Effect of Macrophage-Derived Apolipoprotein E on Established Atherosclerosis in Apolipoprotein E–Deficient Mice

Weibin Shi; Xuping Wang; Nicholas J. Wang; William H. McBride; Aldons J. Lusis

From the Department of Medicine (W.S., X.W., N.J.W., A.J.L.), Department of Microbiology and Molecular Genetics, and the Department of Radiation Oncology (W.H.M.), School of Medicine, University of California, Los Angeles.

Correspondence to Aldons J. Lusis, Department of Medicine, UCLA School of Medicine, 47-123 CHS, Los Angeles, CA 90095-1679. E-mail jlusis{at}medicine.medsch.ucla.edu

Abstract—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 µm² (mean±SEM, n=8) and 12 211±1433 µm² (n=9), respectively, values not significantly different from the lesion areas of the baseline mice (12 347±2487 µm²; n=12, P>0.05). In contrast, apoE^-/- mice reconstituted with apoE^-/- bone marrow developed severe atherosclerotic lesions (453 036±29 767 µm², 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.

Key Words: atherosclerosis • macrophages • apolipoprotein E • regression • bone marrow transplantation

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