Beta-adrenoceptor blockade markedly attenuates transgene expression from cytomegalovirus promoters within the cardiovascular system

Husein K. Salem, Parisa Ranjzad, Anita Driessen, Clare E. Appleby, Anthony M. Heagerty, Paul Kingston

    Research output: Contribution to journalArticlepeer-review

    Abstract

    OBJECTIVES - The major immediate-early cytomegalovirus enhancer/promoter (MIECMV), widely used in cardiovascular gene therapy, contains several positively regulatory cAMP response elements (CRE). Catecholamine signaling via β-adrenoceptors might increase transgene expression from MIECMV, and if so, β-blockers may have a detrimental effect on the efficacy of clinical cardiovascular gene therapy strategies. METHODS AND RESULTS - Cultured smooth muscle cells were exposed to isoprenaline, atenolol, or propranolol, alone and in combination before infection with adenoviruses expressing β-galactosidase. β-galactosidase expression was assayed 72 hours later. Isoprenaline increased transgene expression from MIECMV up to 8-fold (P
    Original languageEnglish
    Pages (from-to)2267-2274
    Number of pages7
    JournalArteriosclerosis, Thrombosis, and Vascular Biology
    Volume26
    Issue number10
    DOIs
    Publication statusPublished - Oct 2006

    Keywords

    • β-adrenergic receptor blockers
    • Catecholamines
    • Gene therapy

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