title: Role of fenofibrate in restoring angiogenesis in diabetic and control hind limb ischemic rats.
abstract: In this study, we examined the effect of fenofibrate, an agonist of 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 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 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.
authors.affiliation: Department of Physiology, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Ensieh
authors.initials: E
authors.lastname: Salehi
authors.forename: Majid
authors.initials: M
authors.lastname: Khazaei
authors.forename: Bahman
authors.initials: B
authors.lastname: Rashidi
mesh_terms: D000818:Animals; D003925:Diabetic Angiopathies / Q000188:drug therapy* / Q000378:metabolism*; D011345:Fenofibrate / Q000627:therapeutic use*; D006614:Hindlimb / Q000098:blood supply*; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D007511:Ischemia / Q000188:drug therapy* / Q000378:metabolism*; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D000960:Hypolipidemic Agents; D047495:PPAR gamma; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; D040301:Vascular Endothelial Growth Factor Receptor-2; D011345:Fenofibrate