Inhibition of Neointimal Hyperplasia by External Radiation in Rat Carotid Injury Model-The Possible Role of Intercellular Adhesion Molecule-1 and Vascular Cell Adhesion Molecule-1-

摘要

Background and Objectives Despite significant improvement in the field of angioplasty, restenosis remains a major obstacle to the long-term success of the procedure. Radiation can effectively inhibit neointimal hyperplasia by causing the arrest of mitosis during cell division and limiting proliferation by reducing the number of regenerating clonal progenitors. Balloon injury could induce the cell adhesion molecule, ICAM-1 and VCAM-1, on SMCs and regenerating endothelial cells (ECs). ICAM-1 and/or VCAM-1 may play a role in the progression of neointimal hyperplasia induced by balloon injury and external radiation may effectively inhibit neointimal hyperplasia by attenuating their expression. The purpose of this study was to examine the effect of external radiation against ICAM-1 and VCAM-1 on neointimal hyperplasia after balloon injury in rat carotid arteries. Materials and Methods A standardized carotid balloon catheter arterial injury was produced in 51 rats and external beam radiation with doses from 5-20 Gy were delivered in 28 rats (radiation treated group) at 24 hours after injury. To investigate the effect of the external radiation on neointimal hyperplasia, the intima area and the intima/medial area of arteries were measured at day 14 after injury. The expressions of ICAM-1 and VCAM-1 at day 2, day 7, and day 10 after injury were studied in control group and radiation treated group by immunohistochemistry. Results Means of intimal area and intima/medial ratio in radiation treated group were significantly lower than those in control group and significantly reduced with increasing radiation dosage. At day 2 after injury, medial SMCs of injury group extensively expressed ICAM-1, while it was focally expressed with 10 Gy radiation treated group. At day 7 and day 10 after injury, ICAM-1 expression on medial SMCs was attenuated and neointimal ICAM-1 expression was increased. As compared with control group, ICAM-1 expression after radiation was weak and focal just around the internal elastic lamina. At 2 days after injury, medial SMCs moderately expressed VCAM-1, which was weakly and focally expressed with 10 Gy radiation treated group. At day 7 and day 10 after injury, focal expression of VCAM-1 was noted around the internal elastic lamina, but there was no VCAM-1 expression on neointima with radiation. Conclusion External radiation after carotid arterial injury may potentially inhibit SMC proliferation and neointimal hyperplasia, and balloon injury-induced or upregulated expressions of ICAM-1 and VCAM-1 may be attenuated with external radiation.