کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5943122 | 1574715 | 2016 | 8 صفحه PDF | دانلود رایگان |
- C/EBPβ regulates genes that control hyperlipidemia and inflammation.
- Hematopoietic C/EBPβ deletion in ApoEâ/â mice prevents hyperlipidemia and atherosclerosis.
- C/EBPβ in hematopoietic-derived macrophages is partly responsible for the observed effects.
Background and ObjectiveAtherosclerosis 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 ApoEâ/â mice on hyperlipidemia, inflammatory responses and lesion formation in the aorta.Methods and ResultsApoEâ/â mice were reconstituted with bone marrow cells derived from either WT or C/EBPβâ/â mice and placed on low fat or high fat/high cholesterol diet for 11 weeks. Hematopoietic C/EBPβ deletion in ApoEâ/â 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. ApoEâ/â mice reconstituted with C/EBPβâ/â bone marrow cells also significantly reduced blood cytokine levels and reduced lesion area in aortic sinuses compared with ApoEâ/â 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.ConclusionC/EBPβ in hematopoietic cells is crucial to regulate diet-induced inflammation, hyperlipidemia and atherosclerosis development.
Journal: Atherosclerosis - Volume 250, July 2016, Pages 172-179