Role of fenofibrate in restoring angiogenesis in diabetic and control hind limb ischemic rats

In this study, we examined the effect of fenofibrate, an agonist of peroxisome proliferator-activated receptor alpha (PPAR alpha), on angiogenesis and serum nitric oxide (NO), vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2) in diabetic and control hind limb ischemic rats. Male Wistar rats underwent left hind limb ischemia. The experimental groups consisted of rats: control, diabetic, control receiving fenofibrate (100 mg/kg/day, by gavage) and diabetic receiving fenofibrate. After 21 days, blood samples were taken and capillary density and capillary/fiber ratio of the ischemic hind limb muscle was evaluated by immunohistochemistry. Activation of PPAR alpha by fenofibrate restored neovascularization in diabetic and control hind limb ischemic rats (p < 0.05). Fenofibrate administration significantly increased serum nitrite concentration, the main metabolite of NO, without significant changes in serum VEGF and VEGFR-2 concentrations. It seems that fenofibrate enhances angiogenesis in hind limb ischemia possibly through increasing of NO bioavailability and can be considered for treatment of diabetic peripheral vascular diseases in future human studies.