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Direct intra-cardiomuscular transfer of β2-adrenergic receptor gene augments cardiac output in cardiomyopathic hamsters

Gene Therapy volume 7, pages 2087–2093 (2000)Cite this article

Abstract

In chronic heart failure, down-regulation of β-adrenergic receptor (β-AR) occurs in cardiomyocytes, resulting in low catecholamine response and impaired cardiac function. To correct the irregularity in the β-AR system, β-AR gene was transduced in vivo into failing cardiomyocytes. The Epstein–Barr virus (EBV)-based plasmid vector carrying human β2-AR gene was injected into the left ventricular muscle of Bio14.6 cardiomyopathic hamsters whose β-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 β2-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 β2-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.

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Acknowledgements

We thank Dr M Bouvier for providing the β2-AR cDNA. This work was supported by a grant-in-aid for scientific research from the Ministry of Education, Science and Culture, a grant from the Japan Heart Foundation and IBM Japan Research Grant, and a grant from Japan Foundation of Cardiovascular Research.

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Authors and Affiliations

  1. First Department of Internal Medicine, Research Institute for Neurological Disease and Geriatrics, Kyoto Prefectural University of Medicine, Kamikyo, Kyoto, Japan

    K Tomiyasu, Y Oda & M Kondo

  2. Department of Microbiology, Research Institute for Neurological Disease and Geriatrics, Kyoto Prefectural University of Medicine, Kamikyo, Kyoto, Japan

    M Nomura, E Satoh, J Imanishi & O Mazda

  3. Department of Dynamic Pathology, Research Institute for Neurological Disease and Geriatrics, Kyoto Prefectural University of Medicine, Kamikyo, Kyoto, Japan

    S Fushiki

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  1. K Tomiyasu
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  8. O Mazda
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Tomiyasu, K., Oda, Y., Nomura, M. et al. Direct intra-cardiomuscular transfer of β2-adrenergic receptor gene augments cardiac output in cardiomyopathic hamsters. Gene Ther 7, 2087–2093 (2000). https://doi.org/10.1038/sj.gt.3301329

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