title: 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.
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.
authors.affiliation: Lenox Hill Heart and Vascular Institute and Cardiovascular Research Foundation, New York, New York 10021, USA. nkipshidze@lenoxhill.net
authors.forename: Nicholas N
authors.initials: NN
authors.lastname: Kipshidze
authors.forename: Patrick
authors.initials: P
authors.lastname: Iversen
authors.forename: Han-Soo
authors.initials: HS
authors.lastname: Kim
authors.forename: Hamid
authors.initials: H
authors.lastname: Yiazdi
authors.forename: George
authors.initials: G
authors.lastname: Dangas
authors.forename: Rufus
authors.initials: R
authors.lastname: Seaborn
authors.forename: Gishel
authors.initials: G
authors.lastname: New
authors.forename: Fermin
authors.initials: F
authors.lastname: Tio
authors.forename: Ron
authors.initials: R
authors.lastname: Waksman
authors.forename: Roxana
authors.initials: R
authors.lastname: Mehran
authors.forename: Mykola
authors.initials: M
authors.lastname: Tsapenko
authors.forename: Gregg W
authors.initials: GW
authors.lastname: Stone
authors.forename: Gary S
authors.initials: GS
authors.lastname: Roubin
authors.forename: Sriram
authors.initials: S
authors.lastname: Iyer
authors.forename: Martin B
authors.initials: MB
authors.lastname: Leon
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Moses
mesh_terms: D000818:Animals; D019917:Blood Vessel Prosthesis Implantation; D020099:Coated Materials, Biocompatible / Q000627:therapeutic use*; D017023:Coronary Angiography; D023903:Coronary Restenosis / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000628:therapy*; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D004195:Disease Models, Animal; D005260:Female; D005500:Follow-Up Studies; D008297:Male; D008955:Models, Cardiovascular; D009025:Morpholines / Q000627:therapeutic use*; D060172:Morpholinos; D010767:Phosphorylcholine / Q000627:therapeutic use*; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis* / Q000187:drug effects*; D013223:Statistics as Topic; D015607:Stents; D013552:Swine; D016896:Treatment Outcome; D017539:Tunica Intima / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology
chemical_list: D020099:Coated Materials, Biocompatible; D009025:Morpholines; D060172:Morpholinos; D016271:Proto-Oncogene Proteins c-myc; D010767:Phosphorylcholine