© 1997 by European Society of Cardiology
Copyright © 1997, European Society of Cardiology
Percutaneous delivery of the gax gene inhibits vessel stenosis in a rabbit model of balloon angioplasty
aDivision of Cardiovascular Research, St. Elizabeth's Medical Center and Tufts University School of Medicine, Boston, MA, USA
bRhône-Poulenc Rorer Gencell, Centre de Recherche de Vitry-Alfortville, Vitry-sur-Seine, France
cHôpital Bichat, Service de Cardiologie, Paris, France
dBoston Scientific Corp., Natick, MA, USA
* Corresponding author. Division of Cardiovascular Research, St. Elizabeth's Medical Center, 736 Cambridge St., Boston, MA 02135, USA. Tel.: +1 (617) 562-7501; fax: +1 (617) 562-7506.
Objectives: The expression of gax, an anti-proliferative homeobox gene, is rapidly downregulated in vascular smooth muscle cells (VSMCs) following arterial injury. Here we performed percutaneous adenovirus-mediated gene transfer into the iliac arteries of normal rabbits using a channel balloon catheter to assess the effects of gax overexpression on neointima formation, lumen diameter, reendothelialization and functional vasomotion. Methods: A channel balloon catheter was used to perform both the arterial injury and local gene delivery. In each animal both iliac arteries were randomly assigned to receive either an adenovirus expressing the gax gene (Ad-Gax) or the β-galactosidase gene (Ad-βgal). In a second group of animals arteries were randomly assigned to receive either Ad-βgal or saline. Results: At one month, angiography revealed 36% less luminal narrowing in the Ad-Gax-treated arteries relative to the Ad-βgal-treated control arteries. Histological analysis revealed that the intimal/medial ratio (I/M) was reduced by 56% in the Ad-Gax group. Endothelium-dependent vasomotion was not affected by the gax gene transfer. In the second group, no statistically significant differences were found between the saline and the Ad-βgal-treated vessels for any of these parameters. Conclusions: Percutaneous adenovirus delivery of the gax gene to rabbit iliac arteries following endothelial denudation and vessel wall injury reduces neointimal hyperplasia and luminal stenosis, but does not affect endothelium-dependent vasomotion. This study demonstrates that a VSMC transcription factor can potentially be utilized for the development of a molecular therapy for vascular disorders.
KEYWORDS Ad-βgal, replication-defective adenoviral vector expressing the β-galactosidase gene; Ad-Gax, replication-defective adenoviral vector expressing the gax gene; PBS, phosphate-buffered saline; VSMC, vascular smooth muscle cell; pfu, plaque-forming unit; RSV LTR, Rous sarcoma virus long terminal repeat; CMV, cytomegalovirus
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