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ARDB |
Receptor
Related Reference Detail Information |
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| § Enhancement of cardiac function after adenoviral-mediated in vivo intracoronary beta2-adrenergic receptor gene delivery. |
Maurice JP;
Hata JA;
Shah AS;
White DC;
McDonald PH;
Dolber PC;
Wilson KH;
Lefkowitz RJ;
Glower DD;
Koch WJ;
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| Department of Surgery, The Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA. |
Abstract: |
| Exogenous gene delivery to alter the function of the heart is a potential novel therapeutic strategy for treatment of cardiovascular diseases such as heart failure (HF). Before gene therapy approaches to alter cardiac function can be realized, efficient and reproducible in vivo gene techniques must be established to efficiently transfer transgenes globally to the myocardium. We have been testing the hypothesis that genetic manipulation of the myocardial beta-adrenergic receptor (beta-AR) system, which is impaired in HF, can enhance cardiac function. We have delivered adenoviral transgenes, including the human beta2-AR (Adeno-beta2AR), to the myocardium of rabbits using an intracoronary approach. Catheter-mediated Adeno-beta2AR delivery produced diffuse multichamber myocardial expression, peaking 1 week after gene transfer. A total of 5 x 10(11) viral particles of Adeno-beta2AR reproducibly produced 5- to 10-fold beta-AR overexpression in the heart, which, at 7 and 21 days after delivery, resulted in increased in vivo hemodynamic function compared with control rabbits that received an empty adenovirus. Several physiological parameters, including dP/dtmax as a measure of contractility, were significantly enhanced basally and showed increased responsiveness to the beta-agonist isoproterenol. Our results demonstrate that global myocardial in vivo gene delivery is possible and that genetic manipulation of beta-AR density can result in enhanced cardiac performance. Thus, replacement of lost receptors seen in HF may represent novel inotropic therapy. |
Reference Source: J Clin Invest 104(1):21-9 |
| Publication Date:
1999
Jul |
| Reference Type: Journal Article |
PubmedID: 10393695 |
| Related
Disease:
Congestive Heart Failure, CHF;
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