Circulation, Vol 89, 1922-1928, Copyright © 1994 by American Heart Association
SJ Chen, JM Wilson and DW Muller
BACKGROUND: The efficacy of aorto-coronary vein grafting is limited by
early graft thrombosis and accelerated graft atherosclerosis. Direct
adenovirus-mediated transfer of genes encoding inhibitory proteins may
prevent or slow progression of vein graft disease. METHODS AND RESULTS:
Recombinant adenoviruses containing the cDNA for the marker gene lacZ
(Ad.CMVlacZ) or soluble vascular cell adhesion molecule (sVCAM) (Ad.CB-
sVCAM) were used to infect segments of porcine jugular vein or human
saphenous vein. Ex vivo testing showed expression of the introduced genes
after incubation with Ad.CMVlacZ or Ad.CBsVCAM for periods from 1 to 24
hours, with an increase in transfection efficiency with increasing
incubation time. Porcine jugular veins were then interposed as vascular
grafts in the carotid arteries of four juvenile farm pigs after ex vivo
gene transfer by incubation for 90 to 120 minutes with Ad.CMVlacZ or
Ad.CBsVCAM. sVCAM-transfected carotid vein grafts were placed on one side
and lacZ transfected veins were placed contralaterally as controls. Three
days later, the vein graft segments were resected. Expression of the lacZ
gene was confirmed by X-Gal chromagen staining and visualization by light
and transmission electron microscopy. Gene expression was apparent in all
layers of the vein graft wall, with prominent staining in the adventitia.
sVCAM expression was confirmed by immunohistochemistry and in situ
hybridization. CONCLUSIONS: We conclude that ex vivo gene transfer before
vein grafting is feasible using a replication-deficient recombinant
adenovirus and results in a high level of gene expression in vivo. The
potential for this approach to prevent early vein graft thrombosis or
accelerated vein graft atherosclerosis requires further evaluation.
ARTICLES
Adenovirus-mediated gene transfer of soluble vascular cell adhesion molecule to porcine interposition vein grafts
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0119.
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