Thalidomide as a potent inhibitor of neointimal hyperplasia after balloon injury in rat carotid artery.

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.