Direct intra-cardiomuscular transfer of beta2-adrenergic receptor gene augments cardiac output in cardiomyopathic hamsters.
In chronic heart failure, down-regulation of beta-adrenergic receptor (beta-AR) occurs in cardiomyocytes, resulting in low catecholamine response and impaired cardiac function. To correct the irregularity in the beta-AR system, beta-AR gene was transduced in vivo into failing cardiomyocytes. The Epstein-Barr virus (EBV)-based plasmid vector carrying human beta2-AR gene was injected into the left ventricular muscle of Bio14.6 cardiomyopathic hamsters whose beta-AR is down-regulated in the cardiomyocytes. The echocardiographic examinations revealed that stroke volume (SV) and cardiac output (CO) were significantly elevated at 2 to 4 days after the beta2-AR gene transfer. Systemic loading of isoproterenol increased the cardiac parameters more significantly on day 2 to day 7, indicating that the adrenergic response was augmented by the genetic transduction. The same procedure did not affect the cardiac function of normal hamsters. Immunohistochemical examinations demonstrated human beta2-AR expression in failing cardiomyocytes transduced with the gene. RT-PCR analysis detected mRNA for the transgene in the heart but not in the liver, spleen, or kidney. The procedures may provide a feasible strategy for gene therapy of severe heart failure. Gene Therapy (2000) 7, 2087-2093.
First Department of Internal Medicine, Research Institute for Neurological Disease and Geriatrics, Kyoto Prefectural University of Medicine, Kamikyo, Kyoto 602-8566, Japan.
K
K
Tomiyasu
Y
Y
Oda
M
M
Nomura
E
E
Satoh
S
S
Fushiki
J
J
Imanishi
M
M
Kondo
O
O
Mazda
D000818:Animals; D002908:Chronic Disease; D006224:Cricetinae; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage; D006333:Heart Failure / Q000628:therapy*; D004854:Herpesvirus 4, Human / Q000235:genetics; D007267:Injections; D008647:Mesocricetus; D010957:Plasmids; D011943:Receptors, Adrenergic, beta / Q000235:genetics*; D014161:Transduction, Genetic
D011943:Receptors, Adrenergic, beta