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dc.contributor.author Freeman, K
dc.contributor.author Lerman, I
dc.contributor.author Kranias, EG
dc.contributor.author Bohlmeyer, T
dc.contributor.author Bristow, MR
dc.contributor.author Lefkowitz, RJ
dc.contributor.author Iaccarino, G
dc.contributor.author Koch, WJ
dc.contributor.author Leinwand, LA
dc.coverage.spatial United States
dc.date.accessioned 2012-10-24T17:45:10Z
dc.date.issued 2001-04
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/11306600
dc.identifier.citation J Clin Invest, 2001, 107 (8), pp. 967 - 974
dc.identifier.issn 0021-9738
dc.identifier.uri http://hdl.handle.net/10161/5924
dc.description.abstract The medical treatment of chronic heart failure has undergone a dramatic transition in the past decade. Short-term approaches for altering hemodynamics have given way to long-term, reparative strategies, including beta-adrenergic receptor (betaAR) blockade. This was once viewed as counterintuitive, because acute administration causes myocardial depression. Cardiac myocytes from failing hearts show changes in betaAR signaling and excitation-contraction coupling that can impair cardiac contractility, but the role of these abnormalities in the progression of heart failure is controversial. We therefore tested the impact of different manipulations that increase contractility on the progression of cardiac dysfunction in a mouse model of hypertrophic cardiomyopathy. High-level overexpression of the beta(2)AR caused rapidly progressive cardiac failure in this model. In contrast, phospholamban ablation prevented systolic dysfunction and exercise intolerance, but not hypertrophy, in hypertrophic cardiomyopathy mice. Cardiac expression of a peptide inhibitor of the betaAR kinase 1 not only prevented systolic dysfunction and exercise intolerance but also decreased cardiac remodeling and hypertrophic gene expression. These three manipulations of cardiac contractility had distinct effects on disease progression, suggesting that selective modulation of particular aspects of betaAR signaling or excitation-contraction coupling can provide therapeutic benefit.
dc.format.extent 967 - 974
dc.language eng
dc.relation.ispartof J Clin Invest
dc.relation.isversionof 10.1172/JCI12083
dc.subject Actins
dc.subject Animals
dc.subject Atrial Natriuretic Factor
dc.subject Biomarkers
dc.subject Calcium
dc.subject Calcium Signaling
dc.subject Calcium-Binding Proteins
dc.subject Cardiomyopathy, Hypertrophic
dc.subject Cyclic AMP-Dependent Protein Kinases
dc.subject Disease Models, Animal
dc.subject Disease Progression
dc.subject Female
dc.subject Gene Expression
dc.subject Heart Failure
dc.subject Male
dc.subject Mice
dc.subject Mice, Transgenic
dc.subject Motor Activity
dc.subject Myocardium
dc.subject Myosin Heavy Chains
dc.subject Receptors, Adrenergic, beta-2
dc.subject beta-Adrenergic Receptor Kinases
dc.title Alterations in cardiac adrenergic signaling and calcium cycling differentially affect the progression of cardiomyopathy.
dc.type Journal Article
duke.description.endpage 974 en_US
duke.description.issue 8 en_US
duke.description.startpage 967 en_US
duke.description.volume 107 en_US
dc.relation.journal Journal of Clinical Investigation en_US
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/11306600
pubs.issue 8
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/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 107

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