Catheter‐mediated delivery of adenoviral vectors expressing β‐adrenergic receptor kinase C‐terminus inhibits intimal hyperplasia and luminal stenosis in rabbit iliac arteries

Background Previous studies have shown that incubation of balloon‐injured rat carotid arteries with adenoviral vectors encoding the carboxyl terminus of the β‐adrenergic receptor kinase (Ad2/βARKct) for 30 min reduces neointima formation. However, it is unclear whether this beneficial effect of βARKct could be achieved using a catheter‐based vector delivery system and whether the observed inhibition of neointima formation translated into a reduction of vessel stenosis. Methods In this study, Ad2/βARKct was infused into the balloon‐injured site of rabbit iliac arteries using a porous infusion catheter over 2 min. Twenty‐eight days after gene transfer, angiographic and histological assessments were performed. Results Angiographic and histological assessments indicate significant ( p < 0.05) inhibition of iliac artery neointima formation and lumen stenosis by Ad2/βARKct. Our studies demonstrate that an inhibitory effect of Ad2/βARKct on neointima formation is achievable using a catheter‐based vector delivery system and that the inhibition of neointima formation translates into a gain in the vessel minimal luminal diameter. The extent of inhibition (35%) was comparable to that observed with adenoviral‐mediated expression of thymidine kinase plus ganciclovir treatment, a cytotoxic gene therapy approach for restenosis. Conclusions These results suggest that adenoviral‐mediated gene transfer of βARKct is a clinically viable cytostatic gene therapy strategy for the treatment of restenosis. Copyright © 2004 John Wiley & Sons, Ltd.