Abstract
Background and Objective: 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. Methods and Results: 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. Conclusion: C/EBPβ in hematopoietic cells is crucial to regulate diet-induced inflammation, hyperlipidemia and atherosclerosis development.
Original language | English |
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Pages (from-to) | 172-179 |
Number of pages | 8 |
Journal | Atherosclerosis |
Volume | 250 |
DOIs | |
State | Published - Jul 1 2016 |
Keywords
- Atherosclerosis
- Bile acid
- Cholesterol efflux
- Cytokine
- Hematopoietic stem cell
- Inflammation
- Macrophage foam cells