Show simple item record Maurice, JP Hata, JA Shah, AS White, DC McDonald, PH Dolber, PC Wilson, KH Lefkowitz, RJ Glower, DD Koch, WJ
dc.coverage.spatial United States 2012-10-24T17:38:01Z 1999-07
dc.identifier.citation J Clin Invest, 1999, 104 (1), pp. 21 - 29
dc.identifier.issn 0021-9738
dc.description.abstract Exogenous gene delivery to alter the function of the heart is a potential novel therapeutic strategy for treatment of cardiovascular diseases such as heart failure (HF). Before gene therapy approaches to alter cardiac function can be realized, efficient and reproducible in vivo gene techniques must be established to efficiently transfer transgenes globally to the myocardium. We have been testing the hypothesis that genetic manipulation of the myocardial beta-adrenergic receptor (beta-AR) system, which is impaired in HF, can enhance cardiac function. We have delivered adenoviral transgenes, including the human beta2-AR (Adeno-beta2AR), to the myocardium of rabbits using an intracoronary approach. Catheter-mediated Adeno-beta2AR delivery produced diffuse multichamber myocardial expression, peaking 1 week after gene transfer. A total of 5 x 10(11) viral particles of Adeno-beta2AR reproducibly produced 5- to 10-fold beta-AR overexpression in the heart, which, at 7 and 21 days after delivery, resulted in increased in vivo hemodynamic function compared with control rabbits that received an empty adenovirus. Several physiological parameters, including dP/dtmax as a measure of contractility, were significantly enhanced basally and showed increased responsiveness to the beta-agonist isoproterenol. Our results demonstrate that global myocardial in vivo gene delivery is possible and that genetic manipulation of beta-AR density can result in enhanced cardiac performance. Thus, replacement of lost receptors seen in HF may represent novel inotropic therapy.
dc.format.extent 21 - 29
dc.language eng
dc.relation.ispartof J Clin Invest
dc.relation.isversionof 10.1172/JCI6026
dc.subject Adenoviridae
dc.subject Adrenergic beta-Agonists
dc.subject Animals
dc.subject Cardiac Catheterization
dc.subject Cells, Cultured
dc.subject Coronary Vessels
dc.subject Gene Expression Regulation
dc.subject Genetic Therapy
dc.subject Genetic Vectors
dc.subject Heart Failure
dc.subject Heart Function Tests
dc.subject Humans
dc.subject Injections, Intra-Arterial
dc.subject Isoproterenol
dc.subject Male
dc.subject Myocardium
dc.subject Rabbits
dc.subject Receptors, Adrenergic, beta-2
dc.subject Signal Transduction
dc.title Enhancement of cardiac function after adenoviral-mediated in vivo intracoronary beta2-adrenergic receptor gene delivery.
dc.type Journal Article
duke.description.endpage 29 en_US
duke.description.issue 1 en_US
duke.description.startpage 21 en_US
duke.description.volume 104 en_US
dc.relation.journal Journal of Clinical Investigation en_US
pubs.issue 1
pubs.organisational-group /Duke
pubs.organisational-group /Duke/Faculty
pubs.organisational-group /Duke/School of Medicine
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments/Biochemistry
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Medicine
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Medicine/Medicine, Cardiology
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Pathology
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Surgery
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Surgery/Surgery, Cardiovascular and Thoracic Surgery
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers/Duke Cancer Institute
pubs.organisational-group /Duke/Trinity College of Arts & Sciences
pubs.organisational-group /Duke/Trinity College of Arts & Sciences/Chemistry
pubs.publication-status Published
pubs.volume 104

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