Adenoviral mediated gene transfer to atherosclerotic arteries after balloon angioplasty

Abstract

The purpose of this study was to examine the pattern of catheter-mediated adenoviral gene transfer into atherosclerotic vessels subjected to balloon injury. Atherosclerotic lesions were created in the iliac arteries of New Zealand white rabbits fed with cholesterol. Balloon dilatation was performed at the angiographically defined region of maximal stenosis. Instillation of a recombinant adenoviral vector encoding beta Galactosidase was performed at the angioplasty site with either (1) a double-balloon catheter (n = 7 arterial segments), (2) a hydrogel-coated balloon (n = 3), (3) a perforated balloon (n = 3), or (4) a catheter with an inflatable circumferential helical ring (n = 4). Successful gene transfer reflected by expression of nuclear-localizing beta-galactosidase activity was observed in all sections displaying angioplasty effect. Genetically modified cells were located in pockets within the deep portions of the neointima, the media, and the adventitia immediately adjacent to dissection planes. Gene transfer to an atherosclerotic vessel subjected to balloon angioplasty is feasible with recombinant adenovirus vectors and currently available delivery catheters. The regions of the vessel wall that express the foreign protein are those which contribute most importantly to the proliferative cellular response which characterizes postangioplasty restenosis.