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

Myointimal hyperplasia after percutaneous transluminal coronary angioplasty (PTCA) is a key component of the process of restenosis. The c-myc is a cri tical cell-cycle division protein involved in the formation of neointima. W e evaluated the long-term impact of local delivery of c-myc neutrally charg ed antisense oligonucleotides (Resten-NG) on myointimal hyperplasia after P TCA in a rabbit model. PTCA was performed in the iliac arteries of 25 New Z ealand white rabbits, using a Transport (TM) catheter at 8 atm for 30 sec, three times; 500 mug 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 supp lemented with 0.25% cholesterol for 10 days before and 60 days after PTCA. Angiography was performed at harvest, and vessels were fixed in formalin, p rocessed, and stained with hematoxylin and eosin (H&E) and Movat. Quantitat ive angiography showed that local delivery of antisense c-myc at PTCA reduc ed 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 planimet ry 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). W e conclude that local delivery of Resten-NG inhibited myointimal hyperplasi a after PTCA in cholesterol-fed rabbits for up to 60 days. (C) 2001 Wiley-L iss, Inc.