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Cardiovasc Res. 2017 Sep 1;113(11):1376-1388. doi: 10.1093/cvr/cvx134.

CCAAT/enhancer-binding protein delta promotes intracellular lipid accumulation in M1 macrophages of vascular lesions.

Lai HY1, Hsu LW1, Tsai HH2, Lo YC2, Yang SH3, Liu PY4,5, Wang JM1,2,6,7,8.

Author information

Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Department of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, No. 1 University Rd., Tainan 70101, Taiwan.
Department of Physiology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Division of Cardiology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan.
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Center of Molecular Inflammation Research, National Cheng Kung University, Tainan, Taiwan.
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.



Lipid homeostasis is reprogrammed in the presence of inflammation, which results in excessive lipid accumulation in macrophages, and leads to the formation of lipid-laden foam cells. We aimed to link an inflammation-responsive transcription factor CCAAT/enhancer-binding protein delta (CEBPD) with polarized macrophages and dissect its contribution to lipid accumulation.

Methods and results:

We found that CEBPD protein colocalized with macrophages in human and mouse (C57BL/6, Apoe-/-) atherosclerotic plaques and that Cebpd deficiency in bone marrow cells suppressed atherosclerotic lesions in hyperlipidemic Apoe-/- mice. CEBPD was responsive to modified low-density lipoprotein (LDL) via the p38MAPK/CREB pathway, and it promoted lipid accumulation in M1 macrophages but not in M2 macrophages. CEBPD up-regulated pentraxin 3 (PTX3), which promoted the macropinocytosis of LDL, and down-regulated ATP-binding cassette subfamily A member 1 (ABCA1), which impaired the intracellular cholesterol efflux in M1 macrophages. We further found that simvastatin (a HMG-CoA reductase inhibitor) could target CEBPD to block lipid accumulation in a manner not directly related to its cholesterol-lowering effect in M1 macrophages.


This study underscores how CEBPD functions at the junction of inflammation and lipid accumulation in M1 macrophages. Therefore, CEBPD-mediated lipid accumulation in M1 macrophages could represent a new therapeutic target for the treatment of cardiovascular diseases.


CEBPD; Inflammation; Macrophages; PTX3; Statins

[Indexed for MEDLINE]

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