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-α) 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-α, 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-α 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.
Original language | English (US) |
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Pages (from-to) | 885-891 |
Number of pages | 7 |
Journal | Arteriosclerosis, thrombosis, and vascular biology |
Volume | 24 |
Issue number | 5 |
DOIs | |
State | Published - May 2004 |
Externally published | Yes |
Keywords
- BFGF
- Inflammation
- Neointima
- TNF-α
- Thalidomide
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine