BACKGROUND: Vein graft intimal hyperplasia is associated with changes in G protein expression. The carboxyl terminus of the beta-adrenergic receptor kinase-1 (beta ARKCT) is known to inhibit G beta gamma-mediated mitogen-activated signaling pathways. This study examines the effects of adenoviral-mediated beta ARKCT infection on the development of intimal hyperplasia in vein grafts. METHODS: New Zealand White rabbits underwent bypass grafting of the carotid artery with the jugular vein. Vein grafts were infected with adenoviral vectors encoding for beta ARKCT (n = 19), beta-galactosidase (n = 3), or empty viral constructs (n = 12). In control animals, vein grafting was performed without infection (n = 10). RESULTS: The efficacy of beta ARKCT infection in vein grafts was verified by reverse transcriptase-polymerase chain reaction. X-gal staining of beta-galactosidase-infected vein grafts demonstrated the transgene in cells throughout the vessel wall. Adenoviral infection of vein grafts without gene transfer did not alter wall thicknesses or sensitivities to contractile agonists, compared with control grafts. beta ARKCT infection, however, reduced intimal thickness by 36% (P < .001) and medial thickness by 24% (P < .001), compared with empty viral infection. beta ARKCT-infected vein grafts also demonstrated increased sensitivity in response to contractile agonists. CONCLUSIONS: These results show that inhibition of G beta gamma signaling with adenoviral-mediated beta ARKCT in vivo infection effectively modifies the structural and functional hyperplastic abnormalities in vein grafts.
BACKGROUND: Vein graft intimal hyperplasia is associated with changes in G protein expression. The carboxyl terminus of the beta-adrenergic receptor kinase-1 (beta ARKCT) is known to inhibit G beta gamma-mediated mitogen-activated signaling pathways. This study examines the effects of adenoviral-mediated beta ARKCT infection on the development of intimal hyperplasia in vein grafts. METHODS: New Zealand White rabbits underwent bypass grafting of the carotid artery with the jugular vein. Vein grafts were infected with adenoviral vectors encoding for beta ARKCT (n = 19), beta-galactosidase (n = 3), or empty viral constructs (n = 12). In control animals, vein grafting was performed without infection (n = 10). RESULTS: The efficacy of beta ARKCT infection in vein grafts was verified by reverse transcriptase-polymerase chain reaction. X-gal staining of beta-galactosidase-infected vein grafts demonstrated the transgene in cells throughout the vessel wall. Adenoviral infection of vein grafts without gene transfer did not alter wall thicknesses or sensitivities to contractile agonists, compared with control grafts. beta ARKCT infection, however, reduced intimal thickness by 36% (P < .001) and medial thickness by 24% (P < .001), compared with empty viral infection. beta ARKCT-infected vein grafts also demonstrated increased sensitivity in response to contractile agonists. CONCLUSIONS: These results show that inhibition of G beta gamma signaling with adenoviral-mediated beta ARKCT in vivo infection effectively modifies the structural and functional hyperplastic abnormalities in vein grafts.