title: CYP2J2 Overexpression Increases EETs and Protects Against HFD-Induced Atherosclerosis in ApoE-/- Mice.
abstract: OBJECTIVE
  The aim of the present study was to investigate how cytochrome P450 (CYP)2J2-derived epoxyeicosatrienoic acids (EETs) regulate the AKT1 and FOXO1 and BIM pathway and protect against endothelial apoptosis in the development and progression of atherosclerosis.
  
  
  RESULTS
  Recombinant adeno-associated virus (rAAV)-mediated CYP2J2 overexpression increased EET levels and prevented high-fat diet-induced atherosclerosis in ApoE mice, which was associated with reduced vascular apoptosis. We also observed that CYP2J2 overexpression suppressed the weight gain induced by a high-fat diet. In vitro CYP2J2 overexpression increased EET levels, subsequently preventing tumor necrosis factor-α-induced apoptosis in human umbilical vein endothelial cells (HUVECs), which contributed to the pathogenesis of atherosclerosis. We observed that AKT1 suppressed BIM expression and apoptosis by inhibiting the function of FOXO1 in cultured HUVECs. Furthermore, we found that CYP2J2 overexpression and its metabolic products, EETs, suppressed tumor necrosis factor-α-induced apoptosis through AKT1 and FOXO1 and BIM dependent signaling in HUVECs.
  
  
  CONCLUSIONS
  In summary, we identified a novel molecular mechanism for CYP2J2-derived EETs to protect against atherosclerosis.
authors: The Institute of Hypertension and Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan City, China.
authors: Wanjun
authors: W
authors: Liu
authors: Tao
authors: T
authors: Wang
authors: Xingwei
authors: X
authors: He
authors: Xintian
authors: X
authors: Liu
authors: Bei
authors: B
authors: Wang
authors: Yujian
authors: Y
authors: Liu
authors: Zhuxi
authors: Z
authors: Li
authors: Rong
authors: R
authors: Tan
authors: Chen
authors: C
authors: Ding
authors: Hongjie
authors: H
authors: Wang
authors: Hesong
authors: H
authors: Zeng
mesh_terms: D000818:Animals; D001057:Apolipoproteins E; D017209:Apoptosis / Q000502:physiology; D050197:Atherosclerosis / Q000503:physiopathology*; D002478:Cells, Cultured; D000090762:Cytochrome P-450 CYP2J2; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004195:Disease Models, Animal; D015777:Eicosanoids / Q000378:metabolism*; D000071161:Forkhead Box Protein O1 / Q000378:metabolism*; D008297:Male; D051379:Mice; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015430:Weight Gain
chemical_list: D001057:Apolipoproteins E; C000717350:CYP2J2 protein, human; D015777:Eicosanoids; D000071161:Forkhead Box Protein O1; D014409:Tumor Necrosis Factor-alpha; D003577:Cytochrome P-450 Enzyme System; D000090762:Cytochrome P-450 CYP2J2; D051057:Proto-Oncogene Proteins c-akt