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PLoS One. 2014 Jan 28;9(1):e85341. doi: 10.1371/journal.pone.0085341. eCollection 2014.

Deficiency of CCAAT/enhancer binding protein-epsilon reduces atherosclerotic lesions in LDLR-/- mice.

Author information

1
Division of Hematology and Oncology, Cedars-Sinai Medical Center, University of California Los Angeles (UCLA) School of Medicine, Los Angeles, California, United States of America.
2
Division of Hematology and Oncology, Cedars-Sinai Medical Center, University of California Los Angeles (UCLA) School of Medicine, Los Angeles, California, United States of America ; Department of Biochemisty and Biophysics, Linus Pauling Institute, Oregon State University, Corvallis, Oregon, United States of America.
3
Department of Human Genetics, Department of Medicine, and Department of Microbiology, Molecular Genetics, and Immunology, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, California, United States of America.
4
Department of Medicine/Division of Cardiology, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, California, United States of America.
5
Division of Pediatric Infectious Diseases and Immunology, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
6
Biostatistics and Bioinformatics Research Center, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
7
Division of Hematology and Oncology, Cedars-Sinai Medical Center, University of California Los Angeles (UCLA) School of Medicine, Los Angeles, California, United States of America ; Cancer Science Institute of Singapore and National Cancer Institute, National University of Singapore, Singapore, Singapore.

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.

PMID:
24489659
PMCID:
PMC3904867
DOI:
10.1371/journal.pone.0085341
[Indexed for MEDLINE]
Free PMC Article

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