title: Vinexin β Ablation Inhibits Atherosclerosis in Apolipoprotein E-Deficient Mice by Inactivating the Akt-Nuclear Factor κB Inflammatory Axis.
abstract: Vinexin β is a novel adaptor protein that regulates cellular adhesion, cytoskeletal reorganization, signal transduction, and transcription; however, the exact role that vinexin β plays in atherosclerosis remains unknown.
  
  
  
  Immunoblot analysis showed that vinexin β expression is upregulated in the atherosclerotic lesions of both patients with coronary heart disease and hyperlipemic apolipoprotein E-deficient mice and is primarily localized in macrophages indicated by immunofluorescence staining. The high-fat diet-induced double-knockout mice exhibited lower aortic plaque burdens than apolipoprotein E-/-littermates and decreased macrophage content. Vinexin β deficiency improved plaque stability by attenuating lipid accumulation and increasing smooth muscle cell content and collagen. Moreover, the bone marrow transplant experiment demonstrated that vinexin β deficiency exerts atheroprotective effects in hematopoietic cells. Consistent with these changes, the mRNA expression of proinflammatory cytokines were downregulated in vinexin β-/-apolipoprotein E-/-mice, whereas the anti-inflammatory M2 macrophage markers were upregulated. The immunohistochemical staining and in vitro experiments showed that deficiency of vinexin β inhibited the accumulation of monocytes and the migration of macrophages induced by tumor necrosis factor α-stimulated human umbilical vein endothelial cells as well as macrophage proliferation. Finally, the inhibitory effects exerted by vinexin β deficiency on foam cell formation, nuclear factor κB activation, and inflammatory cytokine expression were largely reversed by constitutive Akt activation, whereas the increased expression of the nuclear factor κB subset promoted by adenoviral vinexin β was dramatically suppressed by inhibition of AKT.
  
  
  
  Vinexin β deficiency attenuates atherogenesis primarily by suppressing vascular inflammation and inactivating Akt-nuclear factor κB signaling. Our data suggest that vinexin β could be a therapeutic target for the treatment of atherosclerosis.
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.|Cardiovascular Research Institute, Wuhan University, Wuhan, China.|Hubei Key Laboratory of Cardiology, Wuhan, China.
authors.forename: Hongjing
authors.initials: H
authors.lastname: Guan
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.|The Institute of Model Animals of Wuhan University, Wuhan, China.|Medical Research Institute, School of Medicine, Wuhan University, Wuhan, China.
authors.forename: Wen-Lin
authors.initials: WL
authors.lastname: Cheng
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.|The Institute of Model Animals of Wuhan University, Wuhan, China.|Medical Research Institute, School of Medicine, Wuhan University, Wuhan, China.
authors.forename: Junhong
authors.initials: J
authors.lastname: Guo
authors.affiliation: Key Laboratory of CVD, Nanjing Medical University, Nanjing, China.
authors.forename: Meng-Lin
authors.initials: ML
authors.lastname: Chao
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.|The Institute of Model Animals of Wuhan University, Wuhan, China.|Medical Research Institute, School of Medicine, Wuhan University, Wuhan, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.|The Institute of Model Animals of Wuhan University, Wuhan, China.|Medical Research Institute, School of Medicine, Wuhan University, Wuhan, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Gong
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.|The Institute of Model Animals of Wuhan University, Wuhan, China.|Medical Research Institute, School of Medicine, Wuhan University, Wuhan, China.
authors.forename: Xue-Yong
authors.initials: XY
authors.lastname: Zhu
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.|The Institute of Model Animals of Wuhan University, Wuhan, China.|Medical Research Institute, School of Medicine, Wuhan University, Wuhan, China.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: She
authors.affiliation: College of Life Science, Wuhan University, Wuhan, China.
authors.forename: Zan
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China lihl@whu.edu.cn.|The Institute of Model Animals of Wuhan University, Wuhan, China.|Medical Research Institute, School of Medicine, Wuhan University, Wuhan, China.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Li
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency; D050197:Atherosclerosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003331:Coronary Vessels / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics*; D058226:Plaque, Atherosclerotic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D016596:Vinculin
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D001057:Apolipoproteins E; D009124:Muscle Proteins; D012333:RNA, Messenger; C486523:SORBS3 protein, human; C117452:Sorbs3 protein, mouse; D016596:Vinculin
keywords: 
  AKT
  ; atherosclerosis; inflammation; vinexin β