Effect of Low Dose External Irradiation on MMP-2 Expression in Rat Carotid Artery Injury Model

ABSTRACT

BACKGROUND AND OBJECTIVES: Brachytherapy is one of the promising therapeutic strategy for the prevention of restenosis. The effects of low dose irradiation (<10 Gy) on neointimal hyperplasia, and on the expression of MMP-2 are unknown. MATERIALS AND METHODS: Sprague-Dawley rats were subjected to a balloon injury to the common carotid artery. An external irradiation dose of 10 Gy was performed on the irradiated group at 24 hours following the balloon injury. The index of neointima, such as the percentage area of stenosis, maximal intimal thickness and intima/media area ratio in the H/E stain, were measured, as was the MMP-2 positivity (100xMMP-2(+) cell number/total cell number) from the immunohistochemical staining, at 15 and 29 days following injury. Western blotting for the MMP-2 were performed at 2, 4, 9, 15 and 29 days following injury. RESULTS: The percentage area of stenosis (22.3+/-10.9% vs. 40.2+/-12.1%), maximal intimal thickness (0.11+/-0.06 mm vs. 0.30+/-0.12 mm) and intima/media area ratio (61.7+/-25.8% vs. 127.4+/-65.8%) were lower in the irradiated group at 15 days following injury (p<0.05). At 29 days following injury, there were no differences between the two groups for the above mentioned indices: 57.4+/-14.0% vs. 45.5+/-2.1%; 0.45+/-0.11 mm vs. 0.41+/-0.12 mm and 158.1+/-24.5% vs. 187.8+/-101.9%, respectively (p=NS). The MMP-2 levels in the control group were higher than those in the irradiated group at 15 days (1.03+/-0.69 vs. 1.61+/-0.55, p<0.05), but the levels in the irradiated group were higher than those in the control group at 29 days following injury (1.16+/-0.28 vs. 0.72+/-0.28, p<0.05). There were no differences in MMP-2 positivity between the two groups at 15 days following injury (95.6+/-4.4% vs. 93.1+/-3.5%, p=NS). At 29 days after injury, the MMP-2 positivity was higher in the irradiated than the control group (69.4+/-9.0% vs. 24.6+/-9.9%, p<0.05). CONCLUSION: 10 Gy of external irradiation transiently inhibited the neointimal hyperplasia, partly due to the transient inhibition of the MMP-2 activity in our rat carotid artery injury model.