• Kenneth M Fish, Dennis Ladage, Yoshiaki Kawase, Ioannis Karakikes, Dongtak Jeong, Hung Ly, Kiyotake Ishikawa, Lahouaria Hadri, Lisa Tilemann, Jochen Muller-Ehmsen, R Jude Samulski, Evangelia G Kranias, and Roger J Hajjar.
• Department of Cardiology, Cardiovascular Research Center, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA.
• Circ Heart Fail. 2013 Mar 1; 6 (2): 310-7.

BackgroundHeart failure is characterized by impaired function and disturbed Ca2+ homeostasis. Transgenic increases in inhibitor-1 activity have been shown to improve Ca2 cycling and preserve cardiac performance in the failing heart. The aim of this study was to evaluate the effect of activating the inhibitor (I-1c) of protein phosphatase 1 (I-1) through gene transfer on cardiac function in a porcine model of heart failure induced by myocardial infarction.Methods And ResultsMyocardial infarction was created by a percutaneous, permanent left anterior descending artery occlusion in Yorkshire Landrace swine (n=16). One month after myocardial infarction, pigs underwent intracoronary delivery of either recombinant adeno-associated virus type 9 carrying I-1c (n=8) or saline (n=6) as control. One month after myocardial infarction was created, animals exhibited severe heart failure demonstrated by decreased ejection fraction (46.4±7.0% versus sham 69.7±8.5%) and impaired (dP/dt)max and (dP/dt)min. Intracoronary injection of AAV9.I-1c prevented further deterioration of cardiac function and led to a decrease in scar size.ConclusionsIn this preclinical model of heart failure, overexpression of I-1c by intracoronary in vivo gene transfer preserved cardiac function and reduced the scar size.

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