title: Txnip ablation reduces vascular smooth muscle cell inflammation and ameliorates atherosclerosis in apolipoprotein E knockout mice.
abstract: OBJECTIVE
  Inflammation of vascular smooth muscle cells (VSMC) is intimately linked to atherosclerosis and other vascular inflammatory disease. Thioredoxin interacting protein (Txnip) is a key regulator of cellular sulfhydryl redox and a mediator of inflammasome activation. The goals of the present study were to examine the impact of Txnip ablation on inflammatory response to oxidative stress in VSMC and to determine the effect of Txnip ablation on atherosclerosis in vivo.
  
  
  RESULTS
  Using cultured VSMC, we showed that ablation of Txnip reduced cellular oxidative stress and increased protection from oxidative stress when challenged with oxidized phospholipids and hydrogen peroxide. Correspondingly, expression of inflammatory markers and adhesion molecules were diminished in both VSMC and macrophages from Txnip knockout mice. The blunted inflammatory response was associated with a decrease in NF-ĸB nuclear translocation. Loss of Txnip in VSMC also led to a dramatic reduction in macrophage adhesion to VSMC. In vivo data from Txnip-ApoE double knockout mice showed that Txnip ablation led to 49% reduction in atherosclerotic lesion in the aortic root and 71% reduction in the abdominal aorta, compared to control ApoE knockout mice.
  
  
  CONCLUSIONS
  Our data show that Txnip plays an important role in oxidative inflammatory response and atherosclerotic lesion development in mice. The atheroprotective effect of Txnip ablation implicates that modulation of Txnip expression may serve as a potential target for intervention of atherosclerosis and inflammatory vascular disease.
authors.affiliation: Division of Cardiology, Department of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Chang Hyun
authors.initials: CH
authors.lastname: Byon
authors.affiliation: Division of Cardiology, Department of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Tieyan
authors.initials: T
authors.lastname: Han
authors.affiliation: Division of Cardiology, Department of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Judy
authors.initials: J
authors.lastname: Wu
authors.affiliation: Division of Cardiology, Department of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA. Electronic address: sthui@mednet.ucla.edu.
authors.forename: Simon T
authors.initials: ST
authors.lastname: Hui
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism / Q000473:pathology; D001018:Aortic Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D058226:Plaque, Atherosclerotic; D015398:Signal Transduction / Q000187:drug effects; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism*
chemical_list: D001057:Apolipoproteins E; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D018836:Inflammation Mediators; D016328:NF-kappa B; C445672:Txnip protein, mouse; D013879:Thioredoxins; D006861:Hydrogen Peroxide
keywords: Atherosclerosis; Inflammation; Oxidative stress