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Intracoronary adenovirus-mediated delivery and overexpression of the beta(2)-adrenergic receptor in the heart : prospects for molecular ventricular assistance.

dc.contributor.author Glower, Donald D Jr
dc.contributor.author Hata, Jonathan Andrew
dc.contributor.author Koch, Walter J
dc.contributor.author Kypson, Alan P
dc.contributor.author Lefkowitz, Robert J
dc.contributor.author Lilly, R Eric
dc.contributor.author Pippen, Anne
dc.contributor.author Shah, AS
dc.contributor.author Silvestry, Scott Christopher
dc.contributor.author Tai, Oliver
dc.coverage.spatial United States
dc.date.accessioned 2013-09-05T18:53:28Z
dc.date.issued 2000-02-01
dc.identifier https://www.ncbi.nlm.nih.gov/pubmed/10653833
dc.identifier.uri http://hdl.handle.net/10161/7825
dc.description.abstract BACKGROUND: Genetic modulation of ventricular function may offer a novel therapeutic strategy for patients with congestive heart failure. Myocardial overexpression of beta(2)-adrenergic receptors (beta(2)ARs) 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 beta(2)AR 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-betaGal) or the beta(2)AR (Adeno-beta(2)AR). 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-beta(2)AR resulted in approximately 10-fold overexpression in a chamber-specific manner. Delivery of Adeno-betaGal did not alter in vivo left ventricular (LV) systolic function, whereas overexpression of beta(2)ARs in the LV improved global LV contractility, as measured by dP/dt(max), 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 beta(2)AR. 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.
dc.language eng
dc.relation.ispartof Circulation
dc.subject Adenoviridae
dc.subject Animals
dc.subject Cardiac Catheterization
dc.subject Coronary Vessels
dc.subject Genetic Therapy
dc.subject Genetic Vectors
dc.subject Heart Rate
dc.subject Heart Ventricles
dc.subject Humans
dc.subject Immunohistochemistry
dc.subject Isoproterenol
dc.subject Male
dc.subject Mice
dc.subject Myocardial Contraction
dc.subject Myocardium
dc.subject Rabbits
dc.subject Receptors, Adrenergic, beta-2
dc.subject Systole
dc.subject Ventricular Function, Left
dc.subject beta-Galactosidase
dc.title Intracoronary adenovirus-mediated delivery and overexpression of the beta(2)-adrenergic receptor in the heart : prospects for molecular ventricular assistance.
dc.type Journal article
pubs.author-url https://www.ncbi.nlm.nih.gov/pubmed/10653833
pubs.begin-page 408
pubs.end-page 414
pubs.issue 4
pubs.organisational-group Basic Science Departments
pubs.organisational-group Biochemistry
pubs.organisational-group Chemistry
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group Medicine
pubs.organisational-group Medicine, Cardiology
pubs.organisational-group Pathology
pubs.organisational-group School of Medicine
pubs.organisational-group Surgery
pubs.organisational-group Surgery, Cardiovascular and Thoracic Surgery
pubs.organisational-group Trinity College of Arts & Sciences
pubs.publication-status Published
pubs.volume 101
dc.identifier.eissn 1524-4539


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