Journal Article

Adenovirus-mediated overexpression of inhibitor kappa B-alpha attenuates postinfarct remodeling in the rat heart

Karola Trescher, Oliver Bernecker, Barbara Fellner, Marian Gyöngyösi, Sigurd Krieger, Rainer DeMartin, Ernst Wolner and Bruno K. Podesser

in European Journal of Cardio-Thoracic Surgery

Published on behalf of European Association for Cardio-Thoracic Surgery

Volume 26, issue 5, pages 960-967
Published in print November 2004 | ISSN: 1010-7940
Published online November 2004 | e-ISSN: 1873-734X | DOI: http://dx.doi.org/10.1016/j.ejcts.2004.07.043
Adenovirus-mediated overexpression of inhibitor kappa B-alpha attenuates postinfarct remodeling in the rat heart

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  • Cardiothoracic Surgery
  • Anatomy
  • Cardiovascular Medicine
  • History of Medicine

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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 Bα-gene (n=10), the physiological inhibitor of the transcription factor nuclear factor kappa B, respectively, of a β-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 IkBα-transfected hearts IkBα-levels were six-fold higher (P≪0.05) than in β-gal transfected hearts. Concerning in vivo hemodynamics IkBα-treated hearts showed reduced systolic and diastolic left ventricular dimensions compared to the β-gal MI-group (systolic 48±4 vs. 66±3mm; diastolic 67±5 vs. 84±6mm; 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 IkBα hearts compared to β-gal MI-hearts. Conclusion: It can be concluded that overexpression of IkBα leads to an improved cardiac function thereby attenuating postinfarct remodeling.

Journal Article.  4504 words.  Illustrated.

Subjects: Cardiothoracic Surgery ; Anatomy ; Cardiovascular Medicine ; History of Medicine

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