Beta-Adrenoceptor Blockade Markedly Attenuates Transgene Expression From Cytomegalovirus Promoters Within the Cardiovascular System

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