Adenovirus-mediated gene transfer of the β2-adrenergic receptor to donor hearts enhances cardiac function

A. P. Kypson, S. C. Hendrickson, S. A. Akhter, K. Wilson, P. H. McDonald, R. E. Lilly, P. C. Dolber, D. D. Glower, R. J. Lefkowitz, W. J. Koch

    Research output: Contribution to journalArticle

    43 Scopus citations

    Abstract

    Gene transfer to modify donor heart function during transplantation has significant therapeutic implications. Recent studies by our laboratory in transgenic mice have shown that overexpression of β2-adrenergic receptors (β2-ARs) leads to significantly enhanced cardiac function. Tuus, we investigated the functional consequences of adenovirus-mediated gene transfer of the human β2-AR in a rat heterotopic heart transplant model. Donor hearts received 1 ml of solution containing 1 x 1010 p.f.u. of adenovirus encoding the β2-AR or an empty adenovirus as a control. Five days after transplantation, basal left ventricular (LV) pressure was measured using an isolated, isovolumic heart perfusion apparatus. A subset of hearts was stimulated with the β2-AR agonist, zinterol. Treatment with the β2-AR virus resulted in global myocardial gene transfer with a six-fold increase in mean β-AR density which corresponded to a significant increase in basal contractility (LV + dP/dt(max), control: 3152.1 ± 286 versus β2-AR, 6250.6* ± 432.5 mmHg/s; n = 10, *P < 0.02). β2-AR overexpressing hearts also had higher contractility after zinterol administration compared with control hearts. Our results indicate that myocardial function of the transplanted heart can be enhanced by the adenovirus-mediated delivery of β2-ARs. Thus, genetic manipulation may offer a novel therapeutic strategy to improve donor heart function in the postoperative setting.

    Original languageEnglish (US)
    Pages (from-to)1298-1304
    Number of pages7
    JournalGene Therapy
    Volume6
    Issue number7
    DOIs
    StatePublished - Jul 1 1999

    Keywords

    • Adenovirus
    • Cariac function
    • Gene therapy
    • Transplantation
    • β-adrenergic receptor

    ASJC Scopus subject areas

    • Molecular Medicine
    • Molecular Biology
    • Genetics

    Fingerprint Dive into the research topics of 'Adenovirus-mediated gene transfer of the β<sub>2</sub>-adrenergic receptor to donor hearts enhances cardiac function'. Together they form a unique fingerprint.

  • Cite this

    Kypson, A. P., Hendrickson, S. C., Akhter, S. A., Wilson, K., McDonald, P. H., Lilly, R. E., Dolber, P. C., Glower, D. D., Lefkowitz, R. J., & Koch, W. J. (1999). Adenovirus-mediated gene transfer of the β2-adrenergic receptor to donor hearts enhances cardiac function. Gene Therapy, 6(7), 1298-1304. https://doi.org/10.1038/sj.gt.3300940