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KMID : 0368120080380040212
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Korean Circulation Journal
2008 Volume.38 No. 4 p.212 ~ p.219
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Effect of High Dose External Irradiation on the Matrix Metalloprotease-2 Expression in a Rat Carotid Artery Injury Model
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Kim Tae-Kyun
Seung Ki-Bae
Choi Kyu-Bo
Jung Hae-Ok
Kim Yong-Joo
Park Chan-Seok
Jang Sung-Won
Park Hun-Jun
Kim Dong-Bin
Kim Pum-Joon
Baek Sang-Hong
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Abstract
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Background and Objectives: Remodeling of the injured arterial wall is dependent on the action of several extracellular proteases, including matrix metalloprotease-2 (MMP-2), and this protein is associated with the migration of vascular smooth muscle cells. The effect of a high dose of external irradiation (20 Gy) on the MMP-2 expression in neointimal hyperplasia is not known.
Subjects and Methods: Sprague-Dawley rats were subjected to balloon injury to the common carotid artery. At 24 hours after injury, 20 Gy external irradiation was done for the irradiated group (n=25) and this was not done for the control group (n=25). The percent area stenosis, the maximal intimal thickness, the intima/media area ratio on H-E staining and the MMP-2 positivity on the immunohistochemical staining were measured. Western blotting and a gelatin zymogram for determining the MMP-2 protein expression were also performed after the injury.
Results: The parameters of neointimal hyperplasia such as the percent area stenosis, the maximal intimal thickness and the intima/media area ratio were 40.2±12.1%, 0.30±0.12 mm and 1.27±0.32, respectively, at 14 days after injury, and these parameters were maintained as a hyperplastic state at 28 days after injury in the control group. There was undetectable neointimal hyperplasia in the irradiated group compared with the control group (p<0.01). Western blotting demonstrated an increase in the MMP-2 protein level beginning 2 to 4 days after injury in the control group, but there was only a transient increase in the MMP-2 level at day 2 after injury in the irradiated group. The gelatin zymogram and immunohistochemical staining also showed the expression of MMP-2 in the control group, but not in the irradiated group.
Conclusion: These findings suggest the suppressed expression of MMP-2 is associated with reduced neointimal hyperplasia in the balloon injury-rat model.
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KEYWORD
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Radiation therapy, Matrix metalloprotease-2, Carotid artery injuries
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