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J. Biol. Chem., Vol. 275, Issue 48, 37324-37332, December 1, 2000
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From 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.
Large Scale Gene Expression Analysis of Cholesterol-loaded
Macrophages*
,
,
,
,
¶
CV Therapeutics Inc. and § Incyte
Genomics Inc., Palo Alto, California 94304
*
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.
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