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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:885.)
© 2004 American Heart Association, Inc.

Vascular Biology

Thalidomide as a Potent Inhibitor of Neointimal Hyperplasia After Balloon Injury in Rat Carotid Artery

Seung-Jung Park; Hyo-Soo Kim; Han-Mo Yang; Kyung-Woo Park; Seock-Won Youn; Soo-In Jeon; Dae-Hee Kim; Bon-Kwon Koo; In-Ho Chae; Dong-Joo Choi; Byung-Hee Oh; Myoung-Mook Lee; Young-Bae Park

From the Cardiovascular Laboratory (S.-J.P., H.-S.K., H.-M.Y., K.-W.P., S.-W.Y., S.-I.J., D.-H.K., B.-K.K., I.-H.C., D.-J.C., B.-H.O., M.-M.L., Y.-B.P.), Clinical Research Institute, Seoul National University Hospital; and the Department of Internal Medicine (S.J.P., H.-S.K., H.-M.Y., K.-W.P., D.-H.K., B.-K.K., I.-H.C., D.-J.C., B.-H.O., M.-M.L., Y.-B.P.), Seoul National University College of Medicine, Seoul, Korea.

Correspondence to Dr Hyo-Soo Kim or Dr Myoung-Mook Lee, Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-dong Chongno-gu, Seoul 110-744 Korea. E-mail hyosoo{at}snu.ac.kr or mmlee@snu.ac.kr

Objective— Inflammation is one of the main pathogeneses of neointimal hyperplasia after coronary intervention. Thalidomide, because of its potent antiinflammatory and immunomodulatory properties, is being re-evaluated in several clinical fields. Therefore, we examined whether thalidomide therapy affects neointimal formation.

Methods and Results— In male Sprague-Dawley rats, 100 mg/kg of either thalidomide or sucrose (control) was administered daily from 3 days before injury to 2 weeks after conventional carotid artery denudation injury. Thalidomide administration resulted in a significant reduction of neointimal formation (neointima to media ratio 1.26±0.29 versus 0.35±0.13, P<0.001) and proliferative activity of vascular smooth muscle cells. In addition, arterial macrophage infiltration and local expressions of tumor necrosis factor alpha (TNF-) and basic fibroblast growth factor (bFGF) in the injured arteries as measured by immunohistochemistry and immunoblot analysis were significantly reduced by thalidomide treatment. Serum TNF-, measured by ELISA, was also significantly reduced in the thalidomide-treated animals compared with controls after injury (856±213 versus 449±68 pg/mL on day 3, P=0.001; 129±34 versus 63±18 pg/mL on day 14, P=0.001), and we observed a good positive correlation between the serum TNF- levels and the severity of neointimal growth.

Conclusions— We found that thalidomide, through its antiinflammatory and antiproliferative effects, significantly inhibits neointimal hyperplasia in balloon-injured rat carotid arteries. Our results suggest a potential role of thalidomide as a potent inhibitor of neointimal formation after angioplasty.

Key Words: neointima • inflammation • thalidomide • TNF- • bFGF

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