Troglitazone improves blood flow by inhibiting neointimal formation after balloon injury in Otsuka Long-Evans Tokushima Fatty rats

Troglitazone (TGZ) is an antidiabetic agent of the thiazolidinedione (TZD) class that potentiates insulin action. In addition to its effects on insulin action, TGZ has an antiproliferative effect on vascular smooth muscle cells (VSMCs), of which proliferation is a prominent feature of retenosis after balloon injury, as well as atherosclerosis. Therefore, we investigated the effects of TGZ on intimal formation and blood flow after balloon injury in insulin-resistant Otsuka Long-Evans Tokushima Fatty (OLETF) rats to see whether the decrease in insulin resistance could minimize VSMC proliferation and could maintain blood flow. OLETF rats, an animal model of type 2 diabetes, develop spontaneous hyperglycemia after the age of 24 weeks. Balloon injury was applied to the left common carotid arteries of the rats with a 2F Fogarty catheter. Two weeks after the balloon injury, blood flow velocity was measured with Doppler ultrasonography, and histomorphometric analyses of the common carotid arteries were performed. The neointimal formation caused by VSMC proliferation was inhibited by TGZ treatment by as much as 80% (0.197 +/- 0.013 mm(2) v 0.157 +/- 0.011 mm(2), P