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  • Title: Thalidomide as a potent inhibitor of neointimal hyperplasia after balloon injury in rat carotid artery.
    Author: Park SJ, Kim HS, Yang HM, Park KW, Youn SW, Jeon SI, Kim DH, Koo BK, Chae IH, Choi DJ, Oh BH, Lee MM, Park YB.
    Journal: Arterioscler Thromb Vasc Biol; 2004 May; 24(5):885-91. PubMed ID: 14988093.
    Abstract:
    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-alpha) 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-alpha, 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-alpha 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.
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