Adenoviral-mediated inhibition of Gβγ signaling limits the hyperplastic response in experimental vein grafts

T. T.T. Huynh, G. Iaccarino, M. G. Davies, E. Svendsen, W. J. Koch, O. Hagen, R. L. Geary, E. E. Moore, R. B. Wait, T. R. Billiar

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22 Scopus citations

Abstract

Background. Vein graft intimal hyperplasia is associated with changes in G protein expression. The carboxyl terminus of the β-adrenergic receptor kinase-1 (βARK(CT)) is known to inhibit Gβγ-mediated mitogen-activated signaling pathways. This study examines the effects of adenoviral-mediated βARK(CT) 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 βARK(CT) (n = 19), β-galactosidase (n = 3), or empty viral constructs (n = 12). In control animals, vein grafting was performed without infection (n = 10). Results. The efficacy of βARK(CT) infection in vein grafts was verified by reverse transcriptase-polymerase chain reaction, X-gal staining of β-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. βARK(CT) infection, however, reduced intimal thickness by 36% (P < .001) and medial thickness by 24% (P < .001), compared with empty viral injection. βARK(CT-infected) vein grafts also demonstrated increased sensitivity in response to contractile agonists. Conclusions. These results show that inhibition of Gβγ signaling with adenoviral-mediated βARK(CT) in vivo infection effectively modifies the structural and functional hyperplastic abnormalities in vein grafts.

Original languageEnglish (US)
Pages (from-to)177-186
Number of pages10
JournalSurgery
Volume124
Issue number2
DOIs
StatePublished - 1998
Externally publishedYes

ASJC Scopus subject areas

  • Surgery

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    Huynh, T. T. T., Iaccarino, G., Davies, M. G., Svendsen, E., Koch, W. J., Hagen, O., Geary, R. L., Moore, E. E., Wait, R. B., & Billiar, T. R. (1998). Adenoviral-mediated inhibition of Gβγ signaling limits the hyperplastic response in experimental vein grafts. Surgery, 124(2), 177-186. https://doi.org/10.1016/S0039-6060(98)70118-7