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Science 17 February 1995:
Vol. 267. no. 5200, pp. 1034 - 1037
DOI: 10.1126/science.7863332
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Articles

Science, Vol 267, Issue 5200, 1034-1037
Copyright © 1995 by American Association for the Advancement of Science

articles

Prevention of atherosclerosis in apolipoprotein E-deficient mice by bone marrow transplantation

MF Linton, JB Atkinson, and S Fazio

Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-2250.

Apolipoprotein E (apoE) deficiency causes severe hyperlipidemia and atherosclerosis in humans and in gene-targeted mice. Although the majority of apoE in plasma is of hepatic origin, apoE is synthesized by a variety of cell types, including macrophages. Because macrophages derive from hematopoietic cells, bone marrow transplantation was used to examine the potential of apoE synthesized by bone marrow-derived cells to correct the hyperlipidemia and atherosclerosis caused by apoE deficiency. After transplantation of bone marrow from mice with the normal apoE gene into apoE-deficient mice, apoE was detected in serum and promoted clearance of lipoproteins and normalization of serum cholesterol levels. ApoE-deficient mice given transplants of normal bone marrow showed virtually complete protection from diet-induced atherosclerosis.


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Arterioscler. Thromb. Vasc. Biol. 20, 2261-2266
   Abstract »    Full Text »    PDF »
Role of Macrophage-Derived Lipoprotein Lipase in Lipoprotein Metabolism and Atherosclerosis.
M. Van Eck, R. Zimmermann, P. H. E. Groot, R. Zechner, and T. J. C. Van Berkel (2000)
Arterioscler. Thromb. Vasc. Biol. 20 , e53-e62
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Low Levels of Extrahepatic Nonmacrophage ApoE Inhibit Atherosclerosis Without Correcting Hypercholesterolemia in ApoE-Deficient Mice.
F. E. Thorngate, L. L. Rudel, R. L. Walzem, and D. L. Williams (2000)
Arterioscler. Thromb. Vasc. Biol. 20, 1939-1945
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Therapeutic liver repopulation in a mouse model of hypercholesterolemia.
C. Mitchell, A. Mignon, J. E. Guidotti, S. Besnard, M. Fabre, N. Duverger, D. Parlier, A. Tedgui, A. Kahn, and H. Gilgenkrantz (2000)
Hum. Mol. Genet. 9, 1597-1602
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Transport and Processing of Endogenously Synthesized ApoE on the Macrophage Cell Surface.
Y. Zhao and T. Mazzone (2000)
J. Biol. Chem. 275, 4759-4765
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The Heparin-Binding Proteins Apolipoprotein E and Lipoprotein Lipase Enhance Cellular Proteoglycan Production.
J. C. Obunike, S. Pillarisetti, L. Paka, Y. Kako, M. J. Butteri, Y.-Y. Ho, W. D. Wagner, N. Yamada, T. Mazzone, R. J. Deckelbaum, et al. (2000)
Arterioscler. Thromb. Vasc. Biol. 20, 111-118
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Effect of Macrophage-Derived Mouse ApoE, Human ApoE3-Leiden, and Human ApoE2 (Arg158->Cys) on Cholesterol Levels and Atherosclerosis in ApoE-Deficient Mice.
M. Van Eck, N. Herijgers, K. W. Van Dijk, L. M. Havekes, M. H. Hofker, P. H. E. Groot, and T. J. C. Van Berkel (2000)
Arterioscler. Thromb. Vasc. Biol. 20, 119-127
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Apolipoprotein A-I Stimulates Secretion of Apolipoprotein E by Foam Cell Macrophages.
D. Rees, T. Sloane, W. Jessup, R. T. Dean, and L. Kritharides (1999)
J. Biol. Chem. 274, 27925-27933
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Apolipoprotein E-dependent cholesterol efflux from macrophages: kinetic study and divergent mechanisms for endogenous versus exogenous apolipoprotein E.
C.-Y. Lin, H. Duan, and T. Mazzone (1999)
J. Lipid Res. 40, 1618-1627
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Rapid Regression of Atherosclerosis Induced by Liver-Directed Gene Transfer of ApoE in ApoE-Deficient Mice.
K. Tsukamoto, R. Tangirala, S. H. Chun, E. Pure, and D. J. Rader (1999)
Arterioscler. Thromb. Vasc. Biol. 19, 2162-2170
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Determination of the lower threshold of apolipoprotein E resulting in remnant lipoprotein clearance.
A. H. Hasty, M. F. Linton, L. L. Swift, and S. Fazio (1999)
J. Lipid Res. 40, 1529-1538
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