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.
journal_name
Atherosclerosisjournal_title
Atherosclerosisauthors
Rahman SM,Baquero KC,Choudhury M,Janssen RC,de la Houssaye BA,Sun M,Miyazaki-Anzai S,Wang S,Moustaid-Moussa N,Miyazaki M,Friedman JEdoi
10.1016/j.atherosclerosis.2016.03.040subject
Has Abstractpub_date
2016-07-01 00:00:00pages
172-9eissn
0021-9150issn
1879-1484pii
S0021-9150(16)30114-9journal_volume
250pub_type
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