Thrombus generation after adenovirus-mediated gene transfer into atherosclerotic arteries

Thrombosis represents a major issue during arterial local delivery. We eval uated the occurrence of thrombosis after adenovirus (Ad)-mediated gene tran sfer into normal and atherosclerotic arteries. A replication-deficient Ad v ector expressing the beta-galactosidase reporter gene (Ad.RSV beta gal; 4 x 10(9) PFU) was injected into normal and atherosclerotic arteries (n = 11 i n both groups). The contralateral artery received either an Ad vector carry ing no transgene (Ad.MLPnull) (n = 7 in both groups, 4 x 10(9) PFU) or vehi cle buffer (n = 4 in normal group, n = 8 in atherosclerotic group). Animals were sacrificed 3 days following gene transfer for thrombus detection and assessment of beta-galactosidase activity. Thrombus was absent in normal ar teries and in atherosclerotic arteries injected with vehicle buffer only. I n contrast, nonocclusive thrombus was present in atherosclerotic arteries i njected with either Ad.RSV beta gal (5 of 11) or Ad.MLPnull (3 of 7). beta- Galactosidase activity was predominantly found in the endothelial layer of the transfected arteries. Gene transfer and expression occurred despite the presence of the thrombus (4 of 5), and its efficiency did not significantl y differ regardless of the thrombus, We conclude that thrombus frequently o ccurred in atherosclerotic arteries after Ad-mediated gene transfer. Furthe r studies are warranted to identify the mechanisms of thrombus generation a fter Ad-mediated gene transfer into atherosclerotic arteries.