Background and Objectives：Inflammation plays a central role in the development of neointimal hyperplasia. Due to its potent anti-inflammatory property, thalidomide is being re-evaluated in several clinical fields. Thus, we examined whether thalidomide affects neointimal overgrowth.
Materials and Methods：Male Sprague-Dawley rats, pretreated with thalidomide (100 mg/kg qd) for 3 days, underwent carotid artery angioplasty. Thalidomide administration was then continued for 2 weeks after injury.
Results：Compared with the control rats, the systemic inflammatory marker (serum TNF-α) reduced significantly in the thalidomide-treated rats at 3 and 14 days after injury (856±213 vs 449±68 pg/mL, p=0.001, day 3；129±34 vs 63±18 pg/mL, p=0.001, day 14). This effect was accompanied by marked decreases in the arterial macrophage infiltration and by attenuated expressions of TNF-α and bFGF in the arteries, which were measured as local tissue inflammatory indicators. The anti-proliferative effect of thalidomide was confirmed by a reduced number of PCNA-positive vascular smooth muscle cells in the arteries (43.1±2.9 vs 7.4±1.7 %, p<0.001, day14). Morphometric analysis 2 weeks after injury revealed that gains in the luminal area of the thalidomide-treated rats (0.17±0.04 vs 0.05±0.02 mm2, p=0.001) were due to the suppression of neointimal hyperplasia (neointima-to-media[N/M] ratio, 0.35±0.13 vs 1.26±0.29, p<0.001). Moreover, a strong positive correlation was observed between the serum TNF-α and the N/M ratio.
Conclusion：Through its anti-inflammatory and anti-proliferative effect, thalidomide significantly inhibits neointimal hyperplasia. Therefore, thalidomide can be applied in various ways, for instance, as a new drug-eluting stent or as a systemic oral drug against restenosis.
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