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骨髓中的C/EBPβ对于饮食诱导的炎症、胆固醇平衡和动脉粥样硬化至关重要。

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

作者信息

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

机构信息

Department of Nutritional Sciences, Texas Tech University, Lubbock, TX, USA.

Departments of Pediatrics, University of Colorado Denver, Aurora, CO, USA.

出版信息

Atherosclerosis. 2016 Jul;250:172-9. doi: 10.1016/j.atherosclerosis.2016.03.040. Epub 2016 Apr 1.

DOI:10.1016/j.atherosclerosis.2016.03.040
PMID:27072340
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4907836/
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.

摘要

背景与目的

动脉粥样硬化既是一种慢性炎症性疾病，也是一种脂质代谢紊乱疾病。C/EBPβ在造血细胞发育和脂质代谢整合中的作用已有充分记载。然而，C/EBPβ在动脉粥样硬化进展中的作用尚未得到研究。我们评估了ApoE(-/-)小鼠造血细胞中CEBPβ缺失对高脂血症、炎症反应和主动脉病变形成的影响。

方法与结果

用野生型（WT）或C/EBPβ(-/-)小鼠来源的骨髓细胞重建ApoE(-/-)小鼠，并给予低脂或高脂/高胆固醇饮食11周。ApoE(-/-)小鼠造血细胞中C/EBPβ缺失可降低血液和肝脏脂质水平，以及肝脏硬脂酰辅酶A去饱和酶1和脂肪酸合酶的基因表达，而ATP结合盒转运体G1、胆固醇7-α-羟化酶和肝脏X受体α基因的表达显著增加。与用WT骨髓细胞重建的ApoE(-/-)小鼠相比，用C/EBPβ(-/-)骨髓细胞重建的ApoE(-/-)小鼠还显著降低了血液细胞因子水平，并减少了主动脉窦的病变面积。在RAW264.7巨噬细胞中沉默C/EBPβ可防止氧化型低密度脂蛋白（oxLDL）介导的泡沫细胞形成和条件培养基中炎性细胞因子的分泌。

结论

造血细胞中的C/EBPβ对于调节饮食诱导的炎症、高脂血症和动脉粥样硬化发展至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f226/4907836/21b0868a2c16/nihms786638f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f226/4907836/7350bb6506d7/nihms786638f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f226/4907836/551b65960d5c/nihms786638f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f226/4907836/fa6a35d3bfa5/nihms786638f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f226/4907836/146741243fc9/nihms786638f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f226/4907836/21b0868a2c16/nihms786638f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f226/4907836/7350bb6506d7/nihms786638f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f226/4907836/551b65960d5c/nihms786638f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f226/4907836/fa6a35d3bfa5/nihms786638f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f226/4907836/146741243fc9/nihms786638f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f226/4907836/21b0868a2c16/nihms786638f5.jpg

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