title: Local delivery of c-myc neutrally charged antisense oligonucleotides with transport catheter inhibits myointimal hyperplasia and positively affects vascular remodeling in the rabbit balloon injury model.
abstract: Myointimal hyperplasia after percutaneous transluminal coronary angioplasty (PTCA) is a key component of the process of restenosis. The c-myc is a critical cell-cycle division protein involved in the formation of neointima. We evaluated the long-term impact of local delivery of c-myc neutrally charged antisense oligonucleotides (Resten-NG) on myointimal hyperplasia after PTCA in a rabbit model. PTCA was performed in the iliac arteries of 25 New Zealand white rabbits, using a Transport catheter at 8 atm for 30 sec, three times; 500 microg Resten-NG (n = 11) or saline (n = 14) was delivered to the PTCA site at 2 atm with the outer balloon for 2 min. The diet was supplemented with 0.25% cholesterol for 10 days before and 60 days after PTCA. Angiography was performed at harvest, and vessels were fixed in formalin, processed, and stained with hematoxylin and eosin (H&E) and Movat. Quantitative angiography showed that local delivery of antisense c-myc at PTCA reduced late luminal loss from 1.8 +/- 0.30 mm in control animals to 0.90 +/- 0.30 mm in the treatment group (P = 0.001). Histological analysis by planimetry showed that intimal areas were 1.67 +/- 0.44 mm(2) and 0.82 +/- 0.32 mm(2) in the control and antisense delivery groups, respectively (P < 0.05). We conclude that local delivery of Resten-NG inhibited myointimal hyperplasia after PTCA in cholesterol-fed rabbits for up to 60 days.
authors.affiliation: Lenox Hill Heart and Vascular Institute of New York and Cardiovascular Research Foundation, New York, New York 10021, USA. nkipshidze@lenoxhill.net
authors.forename: N
authors.initials: N
authors.lastname: Kipshidze
authors.forename: E
authors.initials: E
authors.lastname: Keane
authors.forename: D
authors.initials: D
authors.lastname: Stein
authors.forename: P
authors.initials: P
authors.lastname: Chawla
authors.forename: V
authors.initials: V
authors.lastname: Skrinska
authors.forename: L R
authors.initials: LR
authors.lastname: Shankar
authors.forename: A
authors.initials: A
authors.lastname: Khanna
authors.forename: R
authors.initials: R
authors.lastname: Komorowski
authors.forename: C
authors.initials: C
authors.lastname: Haudenschild
authors.forename: P
authors.initials: P
authors.lastname: Iversen
authors.forename: M B
authors.initials: MB
authors.lastname: Leon
authors.forename: M H
authors.initials: MH
authors.lastname: Keelan
authors.forename: J
authors.initials: J
authors.lastname: Moses
mesh_terms: D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D000818:Animals; D015153:Blotting, Western; D018929:Cell Culture Techniques; D003251:Constriction, Pathologic / Q000378:metabolism; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D016259:Genes, myc / Q000502:physiology*; D006965:Hyperplasia / Q000378:metabolism; D007083:Iliac Artery / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage* / Q000378:metabolism*; D011817:Rabbits; D013997:Time Factors; D017539:Tunica Intima / Q000293:injuries / Q000378:metabolism* / Q000473:pathology*
chemical_list: D016376:Oligonucleotides, Antisense