The effects of PPARγ agonist rosiglitazone on neointimal hyperplasia in rabbit carotid anastomosis model.
BACKGROUND
Neointimal hyperplasia involving smooth muscle cell (SMC) proliferation, migration and extracellular matrix (ECM) degradation is an important component of atherosclerosis. It develops as a response to vascular injury after balloon angioplasty and vascular graft placement. Matrix metalloproteinases (MMPs) induce SMC proliferation, migration and contribute to intimal hyperplasia by degrading ECM. PPARγ agonists inhibit SMC proliferation, migration and lesion formation. In this study, we aimed to investigate the effects of PPARγ agonist rosiglitazone on neointimal hyperplasia and gelatinase (MMP-2 and MMP-9) expressions in rabbit carotid anastomosis model.


METHODS
New Zealand white rabbits (n = 13, 2.7-3.2 kg) were divided into placebo and treatment groups. Right carotid artery (CA) was transected and both ends were anastomosed. Treatment group (n = 6) received rosiglitazone (3 mg/kg/day/p.o.) and placebo group (n = 7) received PBS (phosphate buffered saline, 2.5 ml/kg/day/p.o.) for 4 weeks postoperatively. After the sacrification, right and left CAs were isolated. Morphometric analyses and immunohistochemical examinations for gelatinases were performed.


RESULTS
Intimal area (0.055 ± 0.005 control vs 0.291 ± 0.020 μm(2) anastomosed, p < 0,05) and index (0.117 ± 0.002 control vs 0.574 ± 0.013 anastomosed, p < 0,01) significantly increased in anastomosed arteries compared to control arteries from placebo group. However, in rosiglitazone-treated group, intimal area (0.291 ± 0.020 PBS vs 0.143 ± 0.027 rosiglitazone, p < 0,05) and index (0.574 ± 0.013 PBS vs 0.263 ± 0.0078 rosiglitazone, p < 0,01) significantly decreased. Furthermore, gelatinase immunopositivity was found to have significantly increased in anastomosed arteries from placebo group and decreased with rosiglitazone treatment.


CONCLUSIONS
These results suggest that rosiglitazone may prevent neointimal hyperplasia, which is the most important factor involved in late graft failure, by inhibiting gelatinase enzyme expression.
Department of Cardiovascular Surgery, Faculty of Medicine, İzmir University, Izmir, Turkey. mehmetguzeloglu@hotmail.com
Mehmet
M
Guzeloglu
Buket
B
Reel
Soner
S
Atmaca
Alper
A
Bagrıyanık
Eyup
E
Hazan
D000704:Analysis of Variance; D000714:Anastomosis, Surgical / Q000379:methods*; D000818:Animals; D006348:Cardiac Surgical Procedures; D002339:Carotid Arteries / Q000187:drug effects / Q000473:pathology / Q000601:surgery*; D016009:Chi-Square Distribution; D005260:Female; D006965:Hyperplasia; D007150:Immunohistochemistry; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D058426:Neointima / Q000188:drug therapy / Q000473:pathology* / Q000517:prevention & control / Q000628:therapy*; D047495:PPAR gamma / Q000819:agonists*; D011817:Rabbits; D000077154:Rosiglitazone; D018709:Statistics, Nonparametric; D045162:Thiazolidinediones / Q000494:pharmacology*
D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D020782:Matrix Metalloproteinases