Passivation of metallic stents after arterial gene transfer of phVEGF165 inhibits thrombus formation and intimal thickening.
J Am Coll Cardiol
; 29(6): 1371-9, 1997 May.
Article
en En
| MEDLINE
| ID: mdl-9137238
ABSTRACT
OBJECTIVES:
This study sought to test the hypothesis that direct gene transfer of an endothelial cell mitogen could passivate metallic stents by accelerating endothelialization of the prosthesis.BACKGROUND:
Thrombosis and restenosis comprise the principal clinical manifestations of compromised biocompatibility of endovascular stents. Previous studies have demonstrated that endothelial recovery at sites of balloon injury is a critical determinant of consequent intimal thickening and mural thrombus. We therefore investigated the potential for an endothelial cell mitogen delivered as plasmid DNA to optimize stent biocompatibility.METHODS:
Naked plasmid DNA encoding vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF) (phVEGF165) was delivered locally using a hydrogel-coated balloon angioplasty catheter to 16 rabbit iliac arteries in which metallic stents had been placed at the site of balloon injury; the contralateral iliac artery of each rabbit was balloon injured and stented but not transfected.RESULTS:
Stent endothelialization was accelerated by phVEGF165 gene transfer (87.38 +/- 5.06% vs. 33.13 +/- 9.73% [mean +/- SEM] of the planimetered stent surface in the treated vs. contralateral limb, p = 0.005). This was associated with a significant reduction in mural thrombus (3.7 +/- 2.4% vs. 32.7 +/- 9.7%, p = 0.01) at day 7 and intimal thickening (maximal intimal area 0.61 +/- 0.09 vs. 1.44 +/- 0.12 mm2, p < 0.0001) at day 28. No benefit was observed from pCMV-luciferase in 14 similarly instrumented control rabbits.CONCLUSIONS:
These findings indicate that arterial gene transfer of naked plasmid DNA encoding for an endothelial cell mitogen may successfully passivate endovascular stents by accelerating stent endothelialization, thereby reducing in-stent thrombus and obstruction due to intimal thickening.
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Banco de datos:
MEDLINE
Asunto principal:
Trombosis
/
Stents
/
Factores de Crecimiento Endotelial
/
Linfocinas
/
Túnica Íntima
/
Técnicas de Transferencia de Gen
/
Arteria Ilíaca
Límite:
Animals
Idioma:
En
Revista:
J Am Coll Cardiol
Año:
1997
Tipo del documento:
Article
País de afiliación:
Estados Unidos