title: Activation of nuclear factor-kappa B significantly contributes to lumen loss in a rabbit iliac artery balloon angioplasty model.
abstract: BACKGROUND
  To investigate the contribution of inflammation to postangioplasty lumen loss, we used an adenoviral gene therapy approach to inhibit the central inflammatory mediator nuclear factor-kappaB (NF-kappaB) by overexpression of its natural inhibitor, IkappaBalpha.
  
  
  RESULTS
  The adenovirus carrying human IkappaBalpha was applied immediately after balloon dilatation by a double-balloon catheter in a rabbit iliac artery restenosis model. Immunohistochemistry of IkappaBalpha revealed that mainly smooth muscle cells of the media but also cells of the adventitia were transduced and expressed the transgene IkappaB alpha for >/= 8 days. At this time point, intercellular adhesion molecule-1 (30%) and monocyte chemotactic protein-1 (50%) expression, as well as recruitment of macrophages into the wounded area (90%), were significantly reduced in IkappaB alpha-treated vessels. In addition, expression of inhibitor of apoptosis proteins was reduced and the percentage of apoptotic cells was increased compared with control-treated contralateral vessels. Animals killed 5 weeks after treatment exhibited a significantly reduced degree of lumen narrowing (P<0.02) on the side treated with adenovirus IkappaBalpha. The lumen gain of approximately 40% was due to positive remodeling.
  
  
  CONCLUSIONS
  From these data, we conclude that balloon angioplasty-induced activation of NF-kappaB contributes to lumen loss likely via induction of an inflammatory response and a decrease in the rate of apoptosis. These data show for the first time that inflammation mediated by NF-kappaB is involved in postangioplasty lumen narrowing. Specific and more potent inhibitors of NF-kappaB might therefore be a useful therapeutic measure to improve clinical outcome after balloon dilatation.
authors.affiliation: Department of Vascular Biology and Thrombosis Research, University of Vienna, Austria.
authors.forename: J M
authors.initials: JM
authors.lastname: Breuss
authors.forename: M
authors.initials: M
authors.lastname: Cejna
authors.forename: H
authors.initials: H
authors.lastname: Bergmeister
authors.forename: A
authors.initials: A
authors.lastname: Kadl
authors.forename: G
authors.initials: G
authors.lastname: Baumgartl
authors.forename: S
authors.initials: S
authors.lastname: Steurer
authors.forename: Z
authors.initials: Z
authors.lastname: Xu
authors.forename: Y
authors.initials: Y
authors.lastname: Koshelnick
authors.forename: J
authors.initials: J
authors.lastname: Lipp
authors.forename: R
authors.initials: R
authors.lastname: De Martin
authors.forename: U
authors.initials: U
authors.lastname: Losert
authors.forename: J
authors.initials: J
authors.lastname: Lammer
authors.forename: B R
authors.initials: BR
authors.lastname: Binder
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D015901:Angiography, Digital Subtraction; D000800:Angioplasty, Balloon / Q000009:adverse effects; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D015870:Gene Expression; D006083:Graft Occlusion, Vascular / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D020672:I-kappa B Proteins; D007083:Iliac Artery / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020556:Neutrophil Infiltration / Q000187:drug effects; D011817:Rabbits; D019076:Transgenes; D014654:Vascular Patency / Q000187:drug effects
chemical_list: D018932:Chemokine CCL2; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D018799:Intercellular Adhesion Molecule-1; D000072000:NF-KappaB Inhibitor alpha