Korean Circ J.  2004 Apr;34(4):346-355. 10.4070/kcj.2004.34.4.346.

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

• Park SJ
• Kim DH
• Seo JB
• Suh JW
• Yoon CH
• Jo SH
• Kang HJ
• Hwang KK
• Cho YS
• Chung WY
• Chae IH
• Choi DJ
• Kim HS

• KMID: 2294359
• DOI: http://doi.org/10.4070/kcj.2004.34.4.346

Abstract

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-alpha) 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-alpha 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-alpha 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.

Keyword

Inflammation; Coronary restenosis; Thalidomide; Cytokines

MeSH Terms

Angioplasty
Animals
Arteries
Carotid Arteries*
Coronary Restenosis
Cytokines
Drug-Eluting Stents
Humans
Hyperplasia*
Inflammation
Macrophages
Male
Muscle, Smooth, Vascular
Phenobarbital
Rats*
Rats, Sprague-Dawley
Thalidomide*
Tumor Necrosis Factor-alpha
Cytokines
Phenobarbital
Thalidomide
Tumor Necrosis Factor-alpha