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Deficiency of CCAAT/Enhancer Binding Protein-Epsilon Reduces Atherosclerotic Lesions in LDLR-/- Mice

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Title Deficiency of CCAAT/Enhancer Binding Protein-Epsilon Reduces Atherosclerotic Lesions in LDLR-/- Mice
Names Okamoto, Ryoko (creator)
Gery, Sigal (creator)
Gombart, Adrian F. (creator)
Wang, Xuping (creator)
Castellani, Lawrence W. (creator)
Akagi, Tadayuki (creator)
Chen, Shuang (creator)
Arditi, Moshe (creator)
Ho, Quoc (creator)
Lusis, Aldons J. (creator)
Li, Quanlin (creator)
Koeffler, H. Phillip (creator)
Date Issued 2014-01-28 (iso8601)
Note This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by the Public Library of Science. The published article can be found at: http://www.plosone.org/.
Abstract The CCAAT/enhancer binding proteins (C/EBPs) are transcription factors involved in hematopoietic cell development and
induction of several inflammatory mediators. C/EBPε is expressed only in myeloid cells including monocytes/macrophages.
Atherosclerosis is an inflammatory disorder of the vascular wall and circulating immune cells such as monocytes/macrophages. Mice deficient in the low density lipoprotein (LDL) receptor (Ldlr-/-) fed on a high cholesterol diet (HCD)
show elevated blood cholesterol levels and are widely used as models to study human atherosclerosis. In this study, we
generated Ldlr and Cebpe double-knockout (llee) mice and compared their atherogenic phenotypes to Ldlr single deficient
(llEE) mice after HCD. Macrophages from llee mice have reduced lipid uptake by foam cells and impaired phagokinetic
motility in vitro compared to macrophages from llEE mice. Also, compared to llEE mice, llee mice have alterations of lipid
metabolism, and reduced atheroma and obesity, particularly the males. Peritoneal macrophages of llee male mice have
reduced mRNA expression of FABP4, a fatty acid binding protein implicated in atherosclerosis. Overall, our study suggests
that the myeloid specific factor C/EBPε is involved in systemic lipid metabolism and that silencing of C/EBPε could decrease
the development of atherosclerosis.
Genre Article
Access Condition http://creativecommons.org/licenses/by/3.0/us/
Identifier Okamoto R, Gery S, Gombart AF, Wang X, Castellani LW, et al. (2014) Deficiency of CCAAT/Enhancer Binding Protein-Epsilon Reduces Atherosclerotic Lesions in LDLR-/- Mice. PLoS ONE 9(1): e85341. doi:10.1371/journal.pone.0085341

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