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Role of Fenofibrate in Restoring Angiogenesis in Diabetic and Control Hind Limb Ischemic Rats Publisher Pubmed



Salehi E1 ; Khazaei M1 ; Rashidi B2
Authors
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Authors Affiliations
  1. 1. Department of Physiology, Isfahan University of Medical Sciences, Isfahan, Iran
  2. 2. Department of Anatomy, Isfahan University of Medical Sciences, Isfahan, Iran

Source: General Physiology and Biophysics Published:2012


Abstract

In this study, we examined the effect offenofibrate, an agonistof peroxisome proliferator-activated receptor α (PPARα), 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 lef hind limb ischemia. The experimental groups consisted of rats: control, diabetic, control receiving fenofibrate (100 mg/kg/day, by gavage) and diabetic receiving fenofibrate. Afer 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 PPARα 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.
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