C/EBPβ in bone marrow is essential for diet induced inflammation, cholesterol balance, and atherosclerosis

Shaikh M. Rahman, Karalee C. Baquero, Mahua Choudhury, Rachel C. Janssen, Becky A. de la Houssaye, Ming Sun, Shinobu Miyazaki-Anzai, Shu Wang, Naima Moustaid-Moussa, Makoto Miyazaki, Jacob E. Friedman

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

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 languageEnglish (US)
Pages (from-to)172-179
Number of pages8
JournalAtherosclerosis
Volume250
DOIs
StatePublished - Jul 1 2016
Externally publishedYes

Keywords

  • Atherosclerosis
  • Bile acid
  • Cholesterol efflux
  • Cytokine
  • Hematopoietic stem cell
  • Inflammation
  • Macrophage foam cells

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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