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Science 3 June 1994:
Vol. 264. no. 5164, pp. 1471 - 1474
DOI: 10.1126/science.7515194
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Articles

Science, Vol 264, Issue 5164, 1471-1474
Copyright © 1994 by American Association for the Advancement of Science

articles

Inhibition of hepatic chylomicron remnant uptake by gene transfer of a receptor antagonist

TE Willnow, Z Sheng, S Ishibashi, and J Herz

Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235.

The low density lipoprotein receptor-related protein (LRP) has been proposed to mediate in concert with the LDL receptor (LDLR) the uptake of dietary lipoproteins into the hepatocytes. This hypothesis was tested by transient inactivation of LRP in vivo. Receptor-associated protein (RAP), a dominant negative regulator of LRP function, was transferred by an adenoviral vector to the livers of mice lacking LDLR (LDLR-/-). The inactivation of LRP by RAP was associated with a marked accumulation of chylomicron remnants in LDLR-/- mice and to a lesser degree in normal mice, suggesting that both LDLR and LRP are involved in remnant clearance.


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M. S. Nielsen, A. Nykjær, I. Warshawsky, A. L. Schwartz, and Jør. Gliemann (1995)
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M. M. Hussain, T. L. Innerarity, W. J. Brecht, and R. W. Mahley (1995)
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   Abstract »    Full Text »    PDF »
High Affinity Binding of Receptor-associated Protein to Heparin and Low Density Lipoprotein Receptor-related Protein Requires Similar Basic Amino Acid Sequence Motifs.
L. Melman, Z.-f. Cao, S. Rennke, M. P. Marzolo, M. R. Wardell, and G. Bu (2001)
J. Biol. Chem. 276, 29338-29346
   Abstract »    Full Text »    PDF »
Low Density Lipoprotein Receptor-related Protein Is Required for Macrophage-mediated Oxidation of Low Density Lipoprotein by 12/15-Lipoxygenase.
W. Xu, Y. Takahashi, T. Sakashita, T. Iwasaki, H. Hattori, and T. Yoshimoto (2001)
J. Biol. Chem. 276, 36454-36459
   Abstract »    Full Text »    PDF »
Low Density Lipoprotein Receptor-related Protein Mediates Apolipoprotein E Inhibition of Smooth Muscle Cell Migration.
D. K. Swertfeger, G. Bu, and D. Y. Hui (2002)
J. Biol. Chem. 277, 4141-4146
   Abstract »    Full Text »    PDF »
Compared with saturated fatty acids, dietary monounsaturated fatty acids and carbohydrates increase atherosclerosis and VLDL cholesterol levels in LDL receptor-deficient, but not apolipoprotein E-deficient, mice.
M. Merkel, W. Velez-Carrasco, L. C. Hudgins, and J. L. Breslow (2001)
PNAS 98, 13294-13299
   Abstract »    Full Text »    PDF »


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Science. ISSN 0036-8075 (print), 1095-9203 (online)