Show simple item record Shah, AS White, DC Emani, S Kypson, AP Lilly, RE Wilson, K Glower, DD Lefkowitz, RJ Koch, WJ
dc.coverage.spatial United States 2012-10-22T20:21:46Z 2001-03-06
dc.identifier.citation Circulation, 2001, 103 (9), pp. 1311 - 1316
dc.description.abstract BACKGROUND: Genetic manipulation to reverse molecular abnormalities associated with dysfunctional myocardium may provide novel treatment. This study aimed to determine the feasibility and functional consequences of in vivo beta-adrenergic receptor kinase (betaARK1) inhibition in a model of chronic left ventricular (LV) dysfunction after myocardial infarction (MI). METHODS AND RESULTS: Rabbits underwent ligation of the left circumflex (LCx) marginal artery and implantation of sonomicrometric crystals. Baseline cardiac physiology was studied 3 weeks after MI; 5x10(11) viral particles of adenovirus was percutaneously delivered through the LCx. Animals received transgenes encoding a peptide inhibitor of betaARK1 (Adeno-betaARKct) or an empty virus (EV) as control. One week after gene delivery, global LV and regional systolic function were measured again to assess gene treatment. Adeno-betaARKct delivery to the failing heart through the LCx resulted in chamber-specific expression of the betaARKct. Baseline in vivo LV systolic performance was improved in Adeno-betaARKct-treated animals compared with their individual pre-gene delivery values and compared with EV-treated rabbits. Total beta-AR density and betaARK1 levels were unchanged between treatment groups; however, beta-AR-stimulated adenylyl cyclase activity in the LV was significantly higher in Adeno-betaARKct-treated rabbits compared with EV-treated animals. CONCLUSIONS: In vivo delivery of Adeno-betaARKct is feasible in the infarcted/failing heart by coronary catheterization; expression of betaARKct results in marked reversal of ventricular dysfunction. Thus, inhibition of betaARK1 provides a novel treatment strategy for improving the cardiac performance of the post-MI heart.
dc.format.extent 1311 - 1316
dc.language eng
dc.relation.ispartof Circulation
dc.subject Adenoviridae
dc.subject Animals
dc.subject Cyclic AMP-Dependent Protein Kinases
dc.subject Gene Expression
dc.subject Gene Transfer Techniques
dc.subject Heart Ventricles
dc.subject Male
dc.subject Myocardial Infarction
dc.subject Rabbits
dc.subject Transgenes
dc.subject beta-Adrenergic Receptor Kinases
dc.title In vivo ventricular gene delivery of a beta-adrenergic receptor kinase inhibitor to the failing heart reverses cardiac dysfunction.
dc.type Journal Article
duke.description.endpage 1316 en_US
duke.description.issue 9 en_US
duke.description.startpage 1311 en_US
duke.description.volume 103 en_US
dc.relation.journal Circulation en_US
pubs.issue 9
pubs.organisational-group /Duke
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 103
dc.identifier.eissn 1524-4539

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