dc.contributor.author |
Shah, AS |
|
dc.contributor.author |
White, DC |
|
dc.contributor.author |
Emani, S |
|
dc.contributor.author |
Kypson, AP |
|
dc.contributor.author |
Lilly, RE |
|
dc.contributor.author |
Wilson, K |
|
dc.contributor.author |
Glower, DD |
|
dc.contributor.author |
Lefkowitz, RJ |
|
dc.contributor.author |
Koch, WJ |
|
dc.coverage.spatial |
United States |
|
dc.date.accessioned |
2012-10-22T20:21:46Z |
|
dc.date.issued |
2001-03-06 |
|
dc.identifier |
https://www.ncbi.nlm.nih.gov/pubmed/11238278 |
|
dc.identifier.uri |
https://hdl.handle.net/10161/5905 |
|
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.language |
eng |
|
dc.publisher |
Ovid Technologies (Wolters Kluwer Health) |
|
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.contributor.id |
White, DC|0135808 |
|
duke.contributor.id |
Glower, DD|0117604 |
|
duke.contributor.id |
Lefkowitz, RJ|0096962 |
|
duke.description.issue |
9 |
|
duke.description.volume |
103 |
|
dc.relation.journal |
Circulation |
|
pubs.author-url |
https://www.ncbi.nlm.nih.gov/pubmed/11238278 |
|
pubs.begin-page |
1311 |
|
pubs.end-page |
1316 |
|
pubs.issue |
9 |
|
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 |
103 |
|
dc.identifier.eissn |
1524-4539 |
|