Thalidomide as a Potent Inhibitor of Neointimal Hyperplasia after Balloon Injury in Rat Carotid Artery.
10.4070/kcj.2004.34.4.346
- Author:
Seung Jung PARK
1
;
Dae Hee KIM
;
Jae Bin SEO
;
Jung Won SUH
;
Chang Hwan YOON
;
Sang Ho JO
;
Hyun Jae KANG
;
Kyung Kuk HWANG
;
Young Seok CHO
;
Woo Young CHUNG
;
In Ho CHAE
;
Dong Ju CHOI
;
Hyo Soo KIM
Author Information
1. Cardiovascular Laboratory, Seoul National University Hospital, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
Inflammation;
Coronary restenosis;
Thalidomide;
Cytokines
- MeSH:
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
- From:Korean Circulation Journal
2004;34(4):346-355
- CountryRepublic of Korea
- Language:Korean
-
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.
