Effect of High Dose External Irradiation on the Matrix Metalloprotease-2 Expression in a Rat Carotid Artery Injury Model.
10.4070/kcj.2008.38.4.212
- Author:
Tae Kyoon KIM
1
;
Yong Joo KIM
;
Chan Seok PARK
;
Hun Jun PARK
;
Dong Bin KIM
;
Sung Won JANG
;
Pum Joon KIM
;
Hae Ok JUNG
;
Sang Hong BAEK
;
Ki Bae SEUNG
;
Kyu Bo CHOI
Author Information
1. Cardiovascular Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea. whitesh@catholic.ac.kr
- Publication Type:Original Article
- Keywords:
Radiation therapy;
Matrix metalloprotease-2;
Carotid artery injuries
- MeSH:
Animals;
Blotting, Western;
Carotid Arteries;
Carotid Artery Injuries;
Carotid Artery, Common;
Constriction, Pathologic;
Gelatin;
Hyperplasia;
Muscle, Smooth, Vascular;
Peptide Hydrolases;
Rats;
Rats, Sprague-Dawley
- From:Korean Circulation Journal
2008;38(4):212-219
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
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. MATERIALS 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.