Adenovirus-mediated arterial gene transfer does not require prior injury for submaximal gene expression

We investigated whether gene expression in arterial wall following adenovirus-mediated gene transfer would be enhanced by prior injury. We introduced Escherichia coli lacZ into the balloon-injured canine femoral arteries through a double-balloon catheter by either a replication-defective adenovirus or liposome-mediated transfection (lipofection) using an expression plasmid, and quantified beta-galactosidase activity in arterial homogenates harvested 5 days after gene transfer. Gene expression by lipofection was enhanced six-fold when gene transfer was performed at 3 days, instead of 0 days after injury. However, gene expression achieved by adenovirus infection was not significantly changed irrespective of when gene transfer was performed between 0 and 12 days after injury, and beta-galactosidase activity was 25-fold higher than the enhanced value obtained by lipofection performed 3 days after injury. Our study indicates that submaximal gene expression in arterial wall can be achieved when adenovirus-mediated gene transfer is performed at the same time as angioplasty.