β-adrenergic receptor desensitisation – a mechanism for post-exercise reductions in cardiac function

2008 ◽  
pp. 27-29
Author(s):  
Rob Shave ◽  
Keith George ◽  
Emma Hart
Keyword(s):  
Cardiac Function ◽  
Adrenergic Receptor ◽  
Post Exercise ◽  
Receptor Desensitisation

scholarly journals β-Adrenergic receptor desensitization in man: insight into post-exercise attenuation of cardiac function

2006 ◽  
Vol 577 (2) ◽  
pp. 717-725 ◽  
Author(s):  
Emma Hart ◽  
Ellen Dawson ◽  
Peter Rasmussen ◽  
Keith George ◽  
Niels H. Secher ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Adrenergic Receptor ◽  
Receptor Desensitization ◽  
Post Exercise ◽  
Insight Into

Abstract 339: Long-term AAV6-βARKct Myocardial Gene Therapy Improves Cardiac Function Via Restoration Of β-Adrenergic Receptor Signaling And Neurohormonal Status Of The Failing Heart

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Giuseppe Rengo ◽  
Anastasios Lymperopoulos ◽  
Carmela Zincarelli ◽  
Maria Donniacuo ◽  
Stephen Soltys ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Gene Delivery ◽  
Cardiac Function ◽  
Adrenergic Receptor ◽  
Fluorescent Protein ◽  
Heart Function ◽  
Weight Ratio ◽  
Intramyocardial Injection ◽  
Molecular Abnormalities ◽  
Virus Serotype

BACKGROUND: The up-regulation of G protein-coupled receptor kinase-2 (GRK2) that is present in compromised myocardium contributes to dysfunctional β-adrenergic receptor (βAR) signaling and cardiac function in heart failure (HF). The peptide βARKct, which inhibits the activation of GRK2, has been shown in acute gene transfer experiments to rescue HF. This study was designed to evaluate chronic βARKct expression in post-myocardial infarction (MI) induced HF using stable myocardial gene delivery with adeno-associated virus serotype-6 (AAV6). METHODS AND RESULTS: In 12 week post-MI HF rats, we delivered βARKct or as a control, Green Fluorescent Protein, via direct intramyocardial injection. We also treated groups with concurrent administration of metoprolol. We found robust and long-lasting (up to 12 weeks post-delivery) transgene expression in the left ventricle (LV) and βARKct expression resulted in significantly improved global heart function as LV ejection fraction and ±dP/dt were increased, whereas LV end diastolic diameter and pressure were decreased. At the molecular level, cardiac βAR density and cAMP accumulation significantly improved over control groups. Fibrotic and hypertrophy markers, as well as heart-to-body weight ratio were markedly decreased by βARKct gene therapy indicating active reversal of adverse LV remodeling. For the first time, we found that chronic βARKct expression and normalization of cardiac βAR signaling led to a reduction of circulating levels of cardiotoxic neurohormones (catecholamines and aldosterone) demonstrating a potential additive mechanism of GRK2 inhibition. Concomitant metoprolol administration preserved the gain in inotropy achieved by βARKct, suggesting compatibility of these two therapeutic modalities, however, metoprolol alone only prevented the deterioration of cardiac function in HF. CONCLUSIONS : Chronic cardiac βARKct gene therapy for HF treatment via AAV6-mediated intracardiac gene delivery is feasible and results in improved cardiac function accompanied by restoration of βAR molecular abnormalities and amelioration of neurohormonal status of HF. These findings suggest βARKct gene therapy might be clinically applicable and of significant value for human HF treatment. This research has received full or partial funding support from the American Heart Association, AHA Great Rivers Affiliate (Delaware, Kentucky, Ohio, Pennsylvania & West Virginia).

scholarly journals Enhancement of cardiac function after adenoviral-mediated in vivo intracoronary β2-adrenergic receptor gene delivery

1999 ◽  
Vol 104 (1) ◽  
pp. 21-29 ◽  
Author(s):  
John P. Maurice ◽  
Jonathan A. Hata ◽  
Ashish S. Shah ◽  
David C. White ◽  
Patricia H. McDonald ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Cardiac Function ◽  
Adrenergic Receptor ◽  
Receptor Gene ◽  
Β2 Adrenergic Receptor ◽  
Adrenergic Receptor Gene

  Adrenergic receptor desensitisation may serve a cardioprotective role

1992 ◽  
Vol 26 (6) ◽  
pp. 608-614 ◽  
Author(s):  
L.-B. Tan ◽  
I. J Benjamin ◽  
W. A Clark
Keyword(s):  
Adrenergic Receptor ◽  
Receptor Desensitisation

Post-exercise oxidative stress and obesity in postmenopausal women: The role ofbeta3-adrenergic receptor polymorphism

2007 ◽  
Vol 23 (10) ◽  
pp. 597-603 ◽  
Author(s):  
Felicja Lwow ◽  
Katarzyna Dunajska ◽  
Urszula Tworowska ◽  
Diana Jędrzejuk ◽  
Łukasz Łaczmański ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Postmenopausal Women ◽  
Adrenergic Receptor ◽  
Post Exercise ◽  
Receptor Polymorphism

Cardiac function in mice overexpressing the beta-adrenergic receptor kinase or a beta ARK inhibitor

Science ◽  
1995 ◽  
Vol 268 (5215) ◽  
pp. 1350-1353 ◽  
Author(s):  
W. Koch ◽  
H. Rockman ◽  
P Samama ◽  
R. Hamilton ◽  
R. Bond ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Adrenergic Receptor ◽  
Receptor Kinase ◽  
Beta Adrenergic Receptor ◽  
Beta Adrenergic
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