Show simple item record Shah, Ashish Lilly, R. Eric Kypson, Alan Tai, Oliver Hata, Jonathan Andrew Pippen, Anne Silvestry, Scott Christopher Lefkowitz, Robert J. Glower, Donald D. Jr. 2012-10-22T21:13:02Z 2012-10-22T21:13:02Z 2000-02
dc.identifier.citation Shah, A. S., R. E. Lilly, et al. (2000). "Intracoronary Adenovirus-Mediated Delivery and Overexpression of the β2-Adrenergic Receptor in the Heart." Circulation 101(4): 408-414. en_US
dc.description.abstract Background—Genetic modulation of ventricular function may offer a novel therapeutic strategy for patients with congestive heart failure. Myocardial overexpression of β2-adrenergic receptors (β2ARs) has been shown to enhance contractility in transgenic mice and reverse signaling abnormalities found in failing cardiomyocytes in culture. In this study, we sought to determine the feasibility and in vivo consequences of delivering an adenovirus containing the human β2AR cDNA to ventricular myocardium via catheter-mediated subselective intracoronary delivery. Methods and Results—Rabbits underwent percutaneous subselective catheterization of either the left or right coronary artery and infusion of adenoviral vectors containing either a marker transgene (Adeno-βGal) or the β2AR (Adeno-β2AR). Ventricular function was assessed before catheterization and 3 to 6 days after gene delivery. Both left circumflex– and right coronary artery–mediated delivery of Adeno-β2AR resulted in ≈10-fold overexpression in a chamber-specific manner. Delivery of Adeno-βGal did not alter in vivo left ventricular (LV) systolic function, whereas overexpression of β2ARs in the LV improved global LV contractility, as measured by dP/dtmax, at baseline and in response to isoproterenol at both 3 and 6 days after gene delivery. Conclusions—Percutaneous adenovirus-mediated intracoronary delivery of a potentially therapeutic transgene is feasible, and acute global LV function can be enhanced by LV-specific overexpression of the β2AR. Thus, genetic modulation to enhance the function of the heart may represent a novel therapeutic strategy for congestive heart failure and can be viewed as molecular ventricular assistance. en_US
dc.publisher American Heart Association en_US
dc.relation.isversionof doi:10.1161/01.CIR.101.4.408 en_US
dc.subject gene therapy en_US
dc.subject myocardium en_US
dc.subject receptors, adrenergic, β en_US
dc.subject ventricles en_US
dc.subject heart failure en_US
dc.subject signal transduction en_US
dc.title Intracoronary Adenovirus-Mediated Delivery and Overexpression of the β2-Adrenergic Receptor in the Heart en_US
dc.type Article en_US
duke.description.endpage 414 en_US
duke.description.issue 4 en_US
duke.description.startpage 408 en_US
duke.description.volume 101 en_US
dc.relation.journal Circulation en_US

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