Intraarterial beta irradiation induces smooth muscle cell apoptosis and reduces medial cellularity in a hypercholesterolemic rabbit restenosis model

Purpose: Ionizing radiation has been shown to be a powerful inhibitor of ne ointimal hyperplasia following arterial injury in several animal models of post-percutaneous transluminal coronary angioplasty (post-PTCA) restenosis, This was previously shown to be associated with a reduction in smooth musc le cell (SMC) mitotic activity. This study evaluated the effect of intraart erial beta irradiation on the arterial wall SMC density and apoptosis, Methods and Materials: Twenty-five carotid and 7 iliac arteries of hypercho lesterolemic New Zealand white rabbits were injured using the Baumgartner t echnique. The impact of an 18 Gy beta radiation dose administered after bal loon injury was studied and compared to a nonirradiated injured control gro up. The medial SMC density as well as the percentage of apoptotic cells wer e determined at 8 days, 21 days, and 6 weeks after injury using an automate d computer-based software. Apoptotic cells were identified using in situ en d-labeling of fragmented DNA, Results: The values for medial apoptosis in control vs, irradiated arteries were: 0.014 +/- 0.023 vs, 0.23 +/- 0.28%, p = NS, at 8 days; 0.012 +/- 0.0 18 vs, 0.07 +/- 0.07%, p = 0.05, at 21 days; and 0 +/- 0 vs, 0.16 +/- 0.11% , p = 0.03, at 6 weeks. The overall incidence of medial apoptotic cells at all time points was 0.01 +/- 0.017 vs, 0.13 +/- 0.14% in controls and irrad iated arteries respectively, p = 0.004, Medial SMC density was significantl y decreased in irradiated arteries in comparison with controls (p < 0.01 at all time-points), Conclusions: Intraarterial beta irradiation stimulates medial SMC apoptosis in balloon-injured arteries. This, together with a decrease in SMC mitotic activity, contributes to a decrease in the arterial wall cellularity. (C) 2000 Elsevier Science Inc.