Application of hydrostatic pressure facilitates ex vivo adenovirus gene transfer into rabbit aortas

We investigated whether application of hydrostatic pressure facilitates ex vivo adenovirus gene transfer into rabbit aortas. Assay of beta-galactosida se activity was performed in the aortas subjected to adenovirus encoding La cZ gene (Ad-LacZ) transfer. Application of hydrostatic pressure at 8 atmosp heres during Ad-LacZ gene transfer (10(10) pfu/mL, 10 min) to aortic segmen ts resulted in an approximately 4.5-fold increase in transgene efficiency. X-Gal staining showed predominant beta-galactosidase activity in the endoth elial and the adventitial cells in the aorta subjected to pressure-supporte d Ad-LacZ gene transfer. Then we examined the effect of heme oxygenase-l (H O-1), which catabolizes heme to carbon monoxide and biliverdin, by transfer ring adenovirus encoding HO-1 (Ad-HO-1) into rabbit aortas using this press urization system, The Ad-MO-I-infected aortic segment showed a significantl y decreased contractile response to phenylephrine compared to the Ad-LacZ-i nfected aortic segment. Pressure-supported adenovirus gene transfer may inc rease the feasibility of exploiting intraoperative adenovirus-mediated gene transfer. (C) 2000 Academic Press.