Catheter-based prostacyclin synthase gene transfer prevents in-stent restenosis in rabbit atheromatous arteries

Objective: Prostacyclin synthase (PGIS) gene transfer have been shown to accelerate re-endothelialization and prevent neointimal formation in balloon-injured arteries. The aim of this study is to evaluate how overexpression of endogenous prostacyclin exerts those beneficial effects in atheromatous arteries. Methods: New Zealand White Rabbits fed a 0.5% cholesterol diet underwent balloon injury and Palmaz-Schatz stent implantation in the iliac arteries followed PGIS gene (pCMV-PGIS, 200 mug) delivery by the lipotransfection method via Dispatch catheter (n = 6 each). Results: One week after transfection, arterial segments of pCMV-PGIS produced higher levels of 6-keto-PGF1alpha than those of control, pCMV-LacZ (p < 0.05). The levels of vascular endothelial growth factor (VEGF) expression was greater in the vessels of pCMV-PGIS than in those of pCMV-LacZ demonstrated by immunohistochemical analysis and quantitation of Western blotting (1.8-fold, p < 0.05). At 2 weeks, in-stent endothelialization was significantly greater in the vessels of pCMV-PGIS than in those of pCMV-LacZ (p < 0.01). The percentage of BrdU-positive nuclei in the injured arterial segments was lower in vessels of pCMV-PGIS than pCMV-LacZ (p < 0.01). At 4 weeks, PGIS gene transfer reduced the neointimal area by 38% (p < 0.05) and widened the lumen area by 71% (p < 0.01). Conclusion: PGIS gene transfer accelerated re-endothelialization, and attenuated neointimal fort-nation after stent implantation in atheromatous rabbit arteries, at least in part, via increased production of VEGF protein. (C) 2003 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.