PERCUTANEOUS DELIVERY OF THE GAX GENE INHIBITS VESSEL STENOSIS IN A RABBIT MODEL OF BALLOON ANGIOPLASTY

Objectives: The expression of gax, an anti-proliferative homeobox gene , is rapidly downregulated in vascular smooth muscle cells (VSMCs) fol lowing arterial injury. Here we performed percutaneous adenovirus-medi ated gene transfer into the iliac arteries of normal rabbits using a c hannel balloon catheter to assess the effects of gax overexpression on neointima formation, lumen diameter, reendothelialization and functio nal vasomotion. Methods: A channel balloon catheter was used to perfor m both the arterial injury and local gene delivery. In each animal bot h iliac arteries were randomly assigned to receive either an adenoviru s expressing the gax gene (Ad-Gax) or the beta-galactosidase gene (Ad- beta gal). In a second group of animals arteries were randomly assigne d to receive either Ad-beta gal or saline. Results: At one month, angi ography revealed 36% less luminal narrowing in the Ad-Gax-treated arte ries relative to the Ad-beta gal-treated control arteries. Histologica l analysis revealed that the intimal/medial ratio (I/M) was reduced by 56% in the Ad-Gax group. Endothelium-dependent vasomotion was not aff ected by the gax gene transfer. In the second group, no statistically significant differences were found between the saline and the Ad-beta gal-treated vessels for any of these parameters. Conclusions: Percutan eous adenovirus delivery of the gax gene to rabbit iliac arteries foll owing endothelial denudation and vessel wall injury reduces neointimal hyperplasia and luminal stenosis, but does not affect endothelium-dep endent vasomotion. This study demonstrates that a VSMC transcription f actor can potentially be utilized for the development of a molecular t herapy for vascular disorders. (C) 1997 Elsevier Science B.V.