Extracellular superoxide dismutase accelerates endothelial recovery and inhibits in-stent restenosis in stented atherosclerotic Watanabe heritable hyperlipidemic rabbit aorta.
J Am Coll Cardiol
; 50(23): 2249-53, 2007 Dec 04.
Article
em En
| MEDLINE
| ID: mdl-18061074
ABSTRACT
OBJECTIVES:
This study examined whether local gene therapy with extracellular superoxide dismutase (EC-SOD) could inhibit in-stent restenosis in atherosclerotic Watanabe heritable hyperlipidemic rabbits.BACKGROUND:
Stenting causes an acute increase in superoxide anion production and oxidative stress; EC-SOD is a major component of antioxidative defense in blood vessels and has powerful cardioprotective effects in ischemic myocardium.METHODS:
Endothelial denudation and stenting were done in 36 adult (15 to 18 months old) rabbits. Catheter-mediated intramural delivery of clinical good manufacturing practice-grade adenoviruses encoding rabbit EC-SOD were done simultaneously with stenting. Control animals received adenovirus-encoding nuclear-targeted beta-galactosidase (AdLacZ). Circulating markers for oxidative stress (nonesterified 8-iso-prostaglandin F2 alpha) were measured. Analysis of 6-day, 28-day, and 90-day vessel histology, radical production, oxidation-specific epitopes, and expression studies were performed.RESULTS:
The EC-SOD treatment reduced oxidant production in stented vessels compared with control vessels. Early systemic recovery of total SOD activity was observed in the treated rabbits. The EC-SOD significantly accelerated endothelial recovery (67.4% +/- 10.8% vs. 24.2.1% +/- 4.6% at 6 days, p < 0.05; 89.3% +/- 3.7% vs. 45.1% +/- 9.6% at 28 days, p < 0.05), and the beneficial effect involved increased proliferation of regenerating endothelium. The EC-SOD group showed a 61.3% lower (p < 0.05) neointimal formation at 28 days, with a similar, albeit nonsignificant trend at 90 days (1.20 +/- 0.32 mm2 vs. 1.88 +/- 0.24 mm2, p = 0.06).CONCLUSIONS:
The results suggest a central pathogenetic role of oxidation sensitive signaling processes in endothelial recovery and developing in-stent restenosis in atherosclerotic vessels. Local therapy against oxidative stress represents a promising therapeutic strategy in stent-induced vascular injury.
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Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Doenças da Aorta
/
Superóxido Dismutase
/
Stents
/
Sequestradores de Radicais Livres
/
Aterosclerose
/
Oclusão de Enxerto Vascular
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
J Am Coll Cardiol
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Finlândia