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Originally published In Press as doi:10.1074/jbc.M004732200 on September 5, 2000

J. Biol. Chem., Vol. 275, Issue 48, 37324-37332, December 1, 2000
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Large Scale Gene Expression Analysis of Cholesterol-loaded Macrophages*

Dov ShiffmanDagger , Thomas MikitaDagger , Julie T. N. TaiDagger , David P. WadeDagger , J. Gordon Porter§, Jeffrey J. Seilhamer§, Roland Somogyi§, Shoudan Liang§, and Richard M. LawnDagger

From Dagger  CV Therapeutics Inc. and § Incyte Genomics Inc., Palo Alto, California 94304

We conducted large scale gene expression analysis of the response of macrophages to exposure to oxidized low density lipoprotein (Ox-LDL). Much of the vessel wall lesion of atherosclerosis is composed of macrophages that have become engorged with cholesterol. These resulting "foam cells" contribute to the progression of vascular disease through several pathways. As a potential model of foam cell formation, we treated THP-1 cells with 12-O-tetradecanoylphorbol 13-acetate to differentiate them into a macrophage-like phenotype and subsequently treated them with oxidized low density lipoprotein for various time periods. RNA from Ox-LDL treated and time-matched control untreated cells was hybridized to microarrays containing 9808 human genes. 268 genes were found to be at least 2-fold regulated at one or more time points. These regulation patterns were classified into seven clusters of expression profiles. The data is discussed in terms of the overall pattern of gene expression, the thematic classification of the responding genes, and the clustering of functional groups in distinct expression patterns. The magnitude and the temporal patterns of gene expression identified known and novel molecular components of the cellular response that are implicated in the growth, survival, migratory, inflammatory, and matrix remodeling activity of vessel wall macrophages. In particular, the role of nuclear receptors in mediating the gene expression modulation by Ox-LDL is highlighted.


* This research was supported by CV Therapeutics Inc. and Incyte Genomics Inc.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: CV Therapeutics Inc., 3172 Porter Dr., Palo Alto, CA 94304. Tel.: 650-812-9514; Fax: 650-858-2694; E-mail: lawn@cvt.com.


Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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