Advanced c-myc antisense (AVI-4126)-eluting phosphorylcholine-coated stent implantation is associated with complete vascular healing and reduced neointimal formation in the porcine coronary restenosis model

✍ Scribed by Nicholas N. Kipshidze; Patrick Iversen; Han-Soo Kim; Hamid Yiazdi; George Dangas; Rufus Seaborn; Gishel New; Fermin Tio; Ron Waksman; Roxana Mehran; Mykola Tsapenko; Gregg W. Stone; Gary S. Roubin; Sriram Iyer; Martin B. Leon; Jeffrey W. Moses

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 349 KB
• Volume: 61
• Category: Article
• ISSN: 1522-1946
• DOI: 10.1002/ccd.20007

✦ Synopsis

Abstract

An advanced six‐ring morpholino backbone c‐myc antisense (AVI‐4126) was shown to inhibit c‐myc expression and intimal hyperplasia after local catheter delivery in a porcine balloon injury model. The purpose of this study was to investigate the effects of an AVI‐4126‐eluting phosphorylcholine‐coated (PC) stent on c‐myc expression restenosis and vascular healing after stent implantation in porcine coronary arteries. PC stents were loaded with AVI‐4126 using soak trap. Nine pigs underwent AVI‐4126 PC coronary stent implantation (two stents/animal). Two to six hours postprocedure, three pigs were sacrificed and stented segments were analyzed by Western blot for c‐myc expression. In chronic experiments, six pigs (12 stent sites) were sacrificed at 28 days following intervention and vessels were perfusion‐fixed. High‐performance liquid chromatography analysis of plasma samples showed minimal presence of the antisense. Western blot analysis of the stented vessels demonstrated inhibition of c‐myc expression at 2 and 6 hr after procedure. Quantitative histologic morphometry showed that the neointimal area was significantly reduced (by 40%) in the antisense‐coated group compared with control (2.3 ± 0.7 vs. 3.9 ± 0.8 mm^2^, respectively; P = 0.0077). Immunostaining and electron microscopy demonstrated complete endothelialization, without fibrin deposition, thrombosis, or necrosis in all implanted stents. In the porcine coronary model, an advanced c‐myc‐eluting PC stent blocked c‐myc expression and significantly inhibited myointimal hyperplasia and allowed complete reendothelialization and healing response. Catheter Cardiovasc Interv 2004;61:518–527. © 2004 Wiley‐Liss, Inc.