The effects of PPARγ agonist rosiglitazone on neointimal hyperplasia in rabbit carotid anastomosis model

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.Intimal area (0.055？±？0.005 control vs 0.291？±？0.020？μm2 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.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.