title: C/EBPβ in bone marrow is essential for diet induced inflammation, cholesterol balance, and atherosclerosis.
abstract: Atherosclerosis is both a chronic inflammatory disease and a lipid metabolism disorder. C/EBPβ is well documented for its role in the development of hematopoietic cells and integration of lipid metabolism. However, C/EBPβ's role in atherosclerotic progression has not been examined. We assessed the impact of hematopoietic CEBPβ deletion in ApoE(-/-) mice on hyperlipidemia, inflammatory responses and lesion formation in the aorta.
  
  
  
  ApoE(-/-) mice were reconstituted with bone marrow cells derived from either WT or C/EBPβ(-/-) mice and placed on low fat or high fat/high cholesterol diet for 11 weeks. Hematopoietic C/EBPβ deletion in ApoE(-/-) mice reduced blood and hepatic lipids and gene expression of hepatic stearoyl CoA desaturase 1 and fatty acid synthase while expression of ATP binding cassette transporter G1, cholesterol 7-alpha-hydroxylase, and liver X receptor alpha genes were significantly increased. ApoE(-/-) mice reconstituted with C/EBPβ(-/-) bone marrow cells also significantly reduced blood cytokine levels and reduced lesion area in aortic sinuses compared with ApoE(-/-) mice reconstituted with WT bone marrow cells. Silencing of C/EBPβ in RAW264.7 macrophage cells prevented oxLDL-mediated foam cell formation and inflammatory cytokine secretion in conditioned medium.
  
  
  
  C/EBPβ in hematopoietic cells is crucial to regulate diet-induced inflammation, hyperlipidemia and atherosclerosis development.
authors.affiliation: Department of Nutritional Sciences, Texas Tech University, Lubbock, TX, USA. Electronic address: Shaikh.rahman@ttu.edu.
authors.forename: Shaikh M
authors.initials: SM
authors.lastname: Rahman
authors.affiliation: Departments of Pediatrics, University of Colorado Denver, Aurora, CO, USA.
authors.forename: Karalee C
authors.initials: KC
authors.lastname: Baquero
authors.affiliation: Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, Kingsville, TX, USA.
authors.forename: Mahua
authors.initials: M
authors.lastname: Choudhury
authors.affiliation: Departments of Pediatrics, University of Colorado Denver, Aurora, CO, USA.
authors.forename: Rachel C
authors.initials: RC
authors.lastname: Janssen
authors.affiliation: Departments of Pediatrics, University of Colorado Denver, Aurora, CO, USA.
authors.forename: Becky A
authors.initials: BA
authors.lastname: de la Houssaye
authors.affiliation: Department of Nutritional Sciences, Texas Tech University, Lubbock, TX, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Sun
authors.affiliation: Renal and Hypertension, University of Colorado Denver, Aurora, CO, USA.
authors.forename: Shinobu
authors.initials: S
authors.lastname: Miyazaki-Anzai
authors.affiliation: Department of Nutritional Sciences, Texas Tech University, Lubbock, TX, USA.
authors.forename: Shu
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Nutritional Sciences, Texas Tech University, Lubbock, TX, USA.
authors.forename: Naima
authors.initials: N
authors.lastname: Moustaid-Moussa
authors.affiliation: Renal and Hypertension, University of Colorado Denver, Aurora, CO, USA.
authors.forename: Makoto
authors.initials: M
authors.lastname: Miyazaki
authors.affiliation: Departments of Pediatrics, University of Colorado Denver, Aurora, CO, USA; Biochemistry and Molecular Genetics, University of Colorado Denver, Aurora, CO, USA.
authors.forename: Jacob E
authors.initials: JE
authors.lastname: Friedman
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism*; D001853:Bone Marrow / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000378:metabolism; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood*; D017077:Culture Media, Conditioned / Q000737:chemistry; D016207:Cytokines / Q000378:metabolism; D004032:Diet / Q000009:adverse effects*; D005260:Female; D005487:Foam Cells / Q000378:metabolism; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006410:Hematopoiesis; D006949:Hyperlipidemias; D007249:Inflammation / Q000378:metabolism*; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D008099:Liver / Q000201:enzymology; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D000074085:Mice, Knockout, ApoE; D000067996:RAW 264.7 Cells
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D017077:Culture Media, Conditioned; D016207:Cytokines; D008055:Lipids; D002784:Cholesterol
keywords: Atherosclerosis; Bile acid; Cholesterol efflux; Cytokine; Hematopoietic stem cell; Inflammation; Macrophage foam cells