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Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
Published on: May 31, 2016
C/EBPβ in bone marrow is essential for diet induced inflammation, cholesterol balance, and atherosclerosis
Shaikh M Rahman1, Karalee C Baquero2, Mahua Choudhury3
1Department of Nutritional Sciences, Texas Tech University, Lubbock, TX, USA.
Insights
CCAAT/enhancer-binding protein beta (C/EBPβ) in hematopoietic cells is crucial for regulating diet-induced inflammation, hyperlipidemia, and atherosclerosis. Its absence reduces lipid levels, inflammatory responses, and aortic lesion formation.
Area of Science:
- Cardiovascular Biology
- Immunology
- Metabolic Disorders
Background:
- Atherosclerosis is a chronic inflammatory disease linked to lipid metabolism disorders.
- CCAAT/enhancer-binding protein beta (C/EBPβ) influences hematopoietic cell development and lipid metabolism.
- The specific role of C/EBPβ in atherosclerotic progression remains unexamined.
Purpose of the Study:
- To investigate the impact of hematopoietic C/EBPβ deletion on atherosclerosis development.
- To assess the effects on hyperlipidemia, inflammatory responses, and aortic lesion formation in ApoE(-/-) mice.
Main Methods:
- ApoE(-/-) mice were reconstituted with wild-type (WT) or C/EBPβ(-/-) bone marrow cells.
- Mice were fed either a low-fat or high-fat/high-cholesterol diet for 11 weeks.
- C/EBPβ was silenced in RAW264.7 macrophage cells to study foam cell formation and cytokine secretion.
Main Results:
- Hematopoietic C/EBPβ deletion reduced blood and hepatic lipids, altering key lipid metabolism gene expression.
- Cytokine levels were significantly reduced, and aortic lesion area decreased in mice lacking hematopoietic C/EBPβ.
- Silencing C/EBPβ in macrophages prevented oxLDL-mediated foam cell formation and inflammatory cytokine release.
Conclusions:
- C/EBPβ in hematopoietic cells plays a critical role in regulating diet-induced inflammation, hyperlipidemia, and atherosclerosis.
- Targeting C/EBPβ in hematopoietic cells may offer a therapeutic strategy for atherosclerosis.
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.
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