Intracoronary Cytoprotective Gene Therapy: A Study of VEGF-B167 in a Pre-Clinical Animal Model of Dilated Cardiomyopathy.

Autor:	Woitek F; Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania; University of Leipzig-Heart Center, Department of Cardiology/Internal Medicine, Leipzig, Germany., Zentilin L; International Centre for Genetic Engineering and Biotechnology, Trieste, Italy., Hoffman NE; Center for Translational Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania., Powers JC; Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania., Ottiger I; Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania; University of Leipzig-Heart Center, Department of Cardiology/Internal Medicine, Leipzig, Germany., Parikh S; Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania., Kulczycki AM; Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania., Hurst M; Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania., Ring N; International Centre for Genetic Engineering and Biotechnology, Trieste, Italy., Wang T; Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania., Shaikh F; Center for Translational Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania., Gross P; Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania., Singh H; Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania., Kolpakov MA; Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania., Linke A; University of Leipzig-Heart Center, Department of Cardiology/Internal Medicine, Leipzig, Germany., Houser SR; Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania., Rizzo V; Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania., Sabri A; Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania., Madesh M; Center for Translational Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania., Giacca M; International Centre for Genetic Engineering and Biotechnology, Trieste, Italy., Recchia FA; Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania; Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy. Electronic address: fabio.recchia@temple.edu.
Jazyk:	angličtina
Zdroj:	Journal of the American College of Cardiology [J Am Coll Cardiol] 2015 Jul 14; Vol. 66 (2), pp. 139-53.
DOI:	10.1016/j.jacc.2015.04.071
Abstrakt:	Background: Vascular endothelial growth factor (VEGF)-B activates cytoprotective/antiapoptotic and minimally angiogenic mechanisms via VEGF receptors. Therefore, VEGF-B might be an ideal candidate for the treatment of dilated cardiomyopathy, which displays modest microvascular rarefaction and increased rate of apoptosis. Objectives: This study evaluated VEGF-B gene therapy in a canine model of tachypacing-induced dilated cardiomyopathy. Methods: Chronically instrumented dogs underwent cardiac tachypacing for 28 days. Adeno-associated virus serotype 9 viral vectors carrying VEGF-B167 genes were infused intracoronarily at the beginning of the pacing protocol or during compensated heart failure. Moreover, we tested a novel VEGF-B167 transgene controlled by the atrial natriuretic factor promoter. Results: Compared with control subjects, VEGF-B167 markedly preserved diastolic and contractile function and attenuated ventricular chamber remodeling, halting the progression from compensated to decompensated heart failure. Atrial natriuretic factor-VEGF-B167 expression was low in normally functioning hearts and stimulated by cardiac pacing; it thus functioned as an ideal therapeutic transgene, active only under pathological conditions. Conclusions: Our results, obtained with a standard technique of interventional cardiology in a clinically relevant animal model, support VEGF-B167 gene transfer as an affordable and effective new therapy for nonischemic heart failure. (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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