The effect of locally delivered c-myc antisense oligonucleotides combined with intravascular brachytherapy of 188Re liquid-filled balloon therapy on vascular smooth muscle cell proliferation in rabbit iliac arteries after injury with a balloon catheter.

Poststenting restenosis is a significant clinical problem that involves vascular smooth muscle cell (VSMC) proliferation. We primarily investigated the effect of c-myc antisense oligodeoxynucleotides (ASODNs) combined with 188Re radiation therapy on VSMC proliferation in rabbit common iliac arteries injured by the porous balloon catheter to explore the therapeutic potential of the combined therapy for the prevention of restenosis. The iliac arteries in rabbits were injured with balloon catheters, and radiation therapy was carried out with a 2.5 mm balloon catheter filled with 188Re (8 or 15 Gy), and ASODNs (300 microg) were applied to the adventitia introduced using a pluronic gel releasing system and a lipofectin delivery system. After 3 weeks, the animals were killed and defined segments of arteries were sectioned. The histological sections were stained using alpha-actin immunohistochemistry staining. The positive alpha-actin ratios were calculated and analyzed statistically among groups. In contrast to the rate of alpha-actin positive cell staining in the control group, the rate of alpha-actin positive cell staining did not decrease (P > 0.05) in the 188Re-irradiated group (8 Gy). However, in the ASODN-treated group, the 188Re-irradiated group (15 Gy), and the combined ASODN - 188Reirradiated groups (8 or 15 Gy), the ratios had markedly decreased (P < 0.01). The effect of the combined group (ASODNs + 188Re (15 Gy)) provided the lowest level of alpha-actin positive cell staining (P < 0.01). The ASODNs (300 microg) effectively decreased VSMC poliferation. The effect of the 188Re radiation on the VSMCs depended on the dosage. The ASODNs (300 microg) and combined 188Re irradiation effectively lowered VSMC proliferation, and the effect was better than that achieved with any other treatment.