Deficiency of CCAAT/enhancer binding protein-epsilon reduces atherosclerotic lesions in LDLR-/- mice.
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.
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.
Ryoko
R
Okamoto
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.
Sigal
S
Gery
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.
Adrian F
AF
Gombart
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.
Xuping
X
Wang
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.
Lawrence W
LW
Castellani
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.
Tadayuki
T
Akagi
Division of Pediatric Infectious Diseases and Immunology, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
Shuang
S
Chen
Division of Pediatric Infectious Diseases and Immunology, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
Moshe
M
Arditi
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.
Quoc
Q
Ho
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.
Aldons J
AJ
Lusis
Biostatistics and Bioinformatics Research Center, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
Quanlin
Q
Li
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.
H Phillip
HP
Koeffler
D000818:Animals; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism*; D022762:CCAAT-Enhancer-Binding Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D022762:CCAAT-Enhancer-Binding Proteins; D011973:Receptors, LDL