title: Cyclophilin A mediates the ox-LDL-induced activation and apoptosis of macrophages via autophagy.
abstract: BACKGROUND
  Oxidized low-density lipoprotein (ox-LDL) is the most common inflammatory factor that mediates the activation and apoptosis of macrophages. Cyclophilin A (CyPA) is expressed following oxidative stress, hypoxia, and infection. However, the role of CyPA in the activation and apoptosis of macrophages is unclear. The aims of the study were to determine whether CyPA mediates the ox-LDL-induced activation and apoptosis in RAW264.7 cells and to analyze potential mechanisms.
  
  
  RESULTS
  Through Western blot and ELISA test, the expression of CyPA induced by ox-LDL is time-dependent in RAW264.7 cells. Gene silencing of CyPA reduced the generation of lipid droplets in the cytoplasm and downregulated the expression of the surface markers of macrophage activation, namely, CD80, CD86, and major histocompatibility complex class 2 antigen. Cell apoptosis is significantly decreased and the level of anti-apoptosis protein bcl-2 is increased in CyPA silent cells compared with the control group. Finally, autophagy-related protein LC3-II/LC3-I ratio level significantly decreased in CyPA silent cells with less autophagosome formation while the blocked autophagy flux was recovered. The differences in the activation and apoptosis between CyPA silent cells and the control cells were inhibited by pre-treatment with class III PI 3-kinase inhibitor 3-MA.
  
  
  CONCLUSIONS
  These results indicate that CyPA mediates the ox-LDL-induced activation and apoptosis in RAW264.7 cells by regulating autophagy.
authors.affiliation: Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, People's Republic of China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Xue
authors.affiliation: Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, People's Republic of China. Electronic address: yuanwei1@medmail.com.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Yuan
authors.affiliation: Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, People's Republic of China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, People's Republic of China.
authors.forename: Jiayi
authors.initials: J
authors.lastname: Weng
authors.affiliation: Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, People's Republic of China.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, People's Republic of China.
authors.forename: Xinru
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, People's Republic of China.
authors.forename: Zhongqun
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, People's Republic of China. Electronic address: yanjinchuan@hotmail.com.
authors.forename: Jinchuan
authors.initials: J
authors.lastname: Yan
mesh_terms: D017209:Apoptosis; D050197:Atherosclerosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001343:Autophagy / Q000187:drug effects*; D015153:Blotting, Western; D002478:Cells, Cultured; D021984:Cyclophilin A / Q000096:biosynthesis / Q000235:genetics*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008854:Microscopy, Electron; D018384:Oxidative Stress / Q000187:drug effects; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D012313:RNA; D021984:Cyclophilin A
keywords: Apoptosis; Atherosclerosis; Autophagy; CyclophilinA; Macrophages; Oxidized low-density lipoprotein