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CCAAT/enhancer-binding protein delta promotes intracellular lipid accumulation in M1 macrophages of vascular lesions.
Lai, Hong-Yue; Hsu, Ling-Wei; Tsai, Hsin-Hwa; Lo, Yu-Chih; Yang, Shang-Hsun; Liu, Ping-Yen; Wang, Ju-Ming.
Afiliación
  • Lai HY; Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
  • Hsu LW; Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
  • Tsai HH; Department of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, No. 1 University Rd., Tainan 70101, Taiwan.
  • Lo YC; Department of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, No. 1 University Rd., Tainan 70101, Taiwan.
  • Yang SH; Department of Physiology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
  • Liu PY; Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
  • Wang JM; Division of Cardiology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan.
Cardiovasc Res ; 113(11): 1376-1388, 2017 Sep 01.
Article en En | MEDLINE | ID: mdl-28859294
AIMS: 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. CONCLUSION: 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteína delta de Unión al Potenciador CCAAT / Células Espumosas / Macrófagos Límite: Animals / Humans Idioma: En Revista: Cardiovasc Res Año: 2017 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteína delta de Unión al Potenciador CCAAT / Células Espumosas / Macrófagos Límite: Animals / Humans Idioma: En Revista: Cardiovasc Res Año: 2017 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Reino Unido