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.


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.
Park
Seung-Jung
SJ
Cardiovascular Laboratory, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea.
Kim
Hyo-Soo
HS
Yang
Han-Mo
HM
Park
Kyung-Woo
KW
Youn
Seock-Won
SW
Jeon
Soo-In
SI
Kim
Dae-Hee
DH
Koo
Bon-Kwon
BK
Chae
In-Ho
IH
Choi
Dong-Joo
DJ
Oh
Byung-Hee
BH
Lee
Myoung-Mook
MM
Park
Young-Bae
YB
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D002339:Carotid Arteries / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D016893:Carotid Stenosis / Q000209:etiology / Q000517:prevention & control; D002404:Catheterization / Q000009:adverse effects*; D004353:Drug Evaluation, Preclinical; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis / Q000097:blood; D006965:Hyperplasia; D007249:Inflammation; D008264:Macrophages / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013792:Thalidomide / Q000494:pharmacology* / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology; D014657:Vasculitis / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control
D000894:Anti-Inflammatory Agents, Non-Steroidal; D014409:Tumor Necrosis Factor-alpha; D016222:Fibroblast Growth Factor 2; D013792:Thalidomide