Effect of Intravascular Irradiation on Cell Proliferation, Apoptosis, and Vascular Remodeling After Balloon Overstretch Injury of Porcine Coronary Arteries

Abstract

Background Ionizing radiation has been shown to reduce vascular lesion formation after balloon overstretch injury of pig coronary arteries. The present series of experiments examines the mechanism by which this occurs. Methods and Results Balloon injury was performed on porcine coronary arteries, followed immediately by ionizing radiation using either a source train of 90 Sr/Y or 192 Ir seeds designed to deliver 14 or 28 Gy at a depth of 2 mm from the source. The animals were killed 3, 7, or 14 days after injury. Bromodeoxyuridine was administered 24 hours before euthanasia to label proliferating cells. Cell proliferation was significantly reduced on day 3 in the adventitia and media of the irradiated vessels compared with controls. Two weeks after injury, there were fewer α-actin–positive myofibroblasts in the adventitia of the irradiated vessels than in nonirradiated controls, and morphometric analysis indicated that the vessel perimeter of the irradiated vessels was significantly larger than in controls. Together, these results suggest a positive effect of intravascular irradiation on vascular remodeling. Apoptosis was estimated by terminal transferase dUTP-biotin nick-end labeling (TUNEL) 3 and 7 days after injury. TUNEL-labeled cells were found primarily in the adventitia at the medial tear, but no differences were detected between irradiated and control vessels. Conclusions These studies suggest that intracoronary radiation primarily inhibits the first wave of cell proliferation in the vessel wall and demonstrates a favorable effect on late remodeling by preventing adventitial fibrosis at the injury site.