title: Adenovirus-mediated overexpression of inhibitor kappa B-alpha attenuates postinfarct remodeling in the rat heart.
abstract: OBJECTIVE
  The transcription factor nuclear factor kappa B (NF-kB) plays an important role in the inflammatory response following myocardial infarction. We hypothesized that NF-kB-blockade in an animal model of acute ischemia reduces the inflammatory response and therefore attenuates ventricular remodeling.
  
  
  METHODS
  Myocardial infarcts (MI) were produced in male Sprague-Dawley rats by ligation of the LAD and followed by adenovirus-mediated intramyocardial delivery of inhibitor kappa Balpha-gene (n=10), the physiological inhibitor of the transcription factor nuclear factor kappa B, respectively, of a beta-gal reporter-gene (n=11). Sham-operated animals (n=10) received neither ligation nor gene transfer. Five days after MI IkB-expression levels were determined by western blotting. Seven weeks after MI in vivo cardiac function was evaluated by transthoracic echocardiography. Based on left ventricular endsystolic and enddiastolic diameters ejection fraction and fractional shortening were calculated. Only animals with MI involving more than 30% of the left ventricle were included. Data are given as mean+/-SD.
  
  
  RESULTS
  In IkBalpha-transfected hearts IkBalpha-levels were six-fold higher (P<0.05) than in beta-gal transfected hearts. Concerning in vivo hemodynamics IkBalpha-treated hearts showed reduced systolic and diastolic left ventricular dimensions compared to the beta-gal MI-group (systolic 48+/-4 vs. 66+/-3 mm; diastolic 67+/-5 vs. 84+/-6 mm; P<0.01). Consequently fractional shortening (27.8+/-1.5 vs. 20.4+/-4.0%; P<0.01) and ejection fraction (63.4+/-3.6 vs. 49.1+/-8.3%; P<0.05) were preserved in IkBalpha hearts compared to beta-gal MI-hearts.
  
  
  CONCLUSIONS
  It can be concluded that overexpression of IkBalpha leads to an improved cardiac function thereby attenuating postinfarct remodeling.
authors.affiliation: Ludwig Boltzmann Institute for Cardiosurgical Research, Medical University of Vienna, Vienna, Austria.
authors.forename: Karola
authors.initials: K
authors.lastname: Trescher
authors.forename: Oliver
authors.initials: O
authors.lastname: Bernecker
authors.forename: Barbara
authors.initials: B
authors.lastname: Fellner
authors.forename: Marian
authors.initials: M
authors.lastname: Gyöngyösi
authors.forename: Sigurd
authors.initials: S
authors.lastname: Krieger
authors.forename: Rainer
authors.initials: R
authors.lastname: Demartin
authors.forename: Ernst
authors.initials: E
authors.lastname: Wolner
authors.forename: Bruno K
authors.initials: BK
authors.lastname: Podesser
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006439:Hemodynamics; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D020257:Ventricular Remodeling
chemical_list: D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606206:Nfkbia protein, rat; D000072000:NF-KappaB Inhibitor alpha