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

Yasushi Numaguchi, Kenji Okumura, Mitsunori Harada, Keiji Naruse, Michiharu Yamada, Hiroyuki Osanai, Hideo Matsui, Masafumi Ito, Toyoaki Murohara

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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 μg) 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-PGF1α 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 formation after stent implantation in atheromatous rabbit arteries, at least in part, via increased production of VEGF protein.

Original languageEnglish
Pages (from-to)177-185
Number of pages9
JournalCardiovascular Research
Volume61
Issue number1
DOIs
Publication statusPublished - Jan 1 2004

Keywords

  • Atherosclerosis
  • Gene therapy
  • Prostaglandins
  • Restenosis
  • Stents

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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