%0 Journal Article
%T Pan-PPAR Agonist, Bezafibrate, Restores Angiogenesis in Hindlimb Ischemia in Normal and Diabetic Rats
%A M. Khazaei
%A E. Salehi
%A B. Rashidi
%J International Journal of Peptides
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/637212
%X Introduction. The aim of this study was to investigate the effect of bezafibrate as a pan-PPAR agonist on angiogenesis and serum nitrite, the main metabolite of nitric oxide (NO), vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2) concentrations in hindlimb ischemia model of normal and type I diabetic rats. Methods. 28 male Wistar rats were divided into control and diabetic groups. Then, all rats underwent unilateral hindlimb ischemia. After recovery, they were randomly assigned to one of the following experimental groups: (1) control; (2) control£¿+£¿bezafibrate (400£¿mg/kg/day); (3) diabetic; (4) diabetic£¿+£¿beztafibrate. After three weeks, blood samples were taken and capillary density was evaluated in the gasterocnemius muscle of ischemic limb. Results. Bezafibrate increased capillary density and capillary/fiber ratio in ischemic leg of diabetic and control rats ( ). Serum VEGF and VEGFR-2 concentrations did not alter after bezafibrate administration, however, serum nitrite concentration was significantly higher in bezafibrate-treated groups than non-treated groups ( ). Discussion. It seems that bezafibrate, as a pan PPAR agonist, restores angiogenesis in hindlimb ischemic diabetic animals and is useful for prevention and/or treatment of peripheral artery disease in diabetic subjects. 1. Introduction Peroxisome proliferator-activated receptors (PPARs) are ligand-inducible transcription factors that regulate expression of genes involved in some biological effects including lipid metabolism, inflammatory responses, and glucose homeostasis [1]. There are three isotypes of PPAR superfamily: PPAR¦Á, PPAR¦Â, and PPAR¦Ã. Today, PPAR agonists have clinical importance in management of dyslipidemia (such as clofibrate, a PPAR¦Á agonist) and reducing insulin resistance and antidiabetic activity (such as rosiglitazone, a PPAR¦Ã agonist). Bezafibrate, a PPAR¦Á agonist, is high-affinity ligand of PPAR¦Ã and PPAR¦Â and is considered as a pan-PPAR agonist [2, 3]. Bezafibrate is more efficient in reducing body weight and blood glucose than fenofibrate in overweight mice fed with high-fat diet [4]. It also raises HDL, reduces triglyceride, and improves insulin sensitivity in diabetic subjects [5, 6]. Diabetes is associated with several cardiovascular abnormalities including abnormal angiogenesis [7]. Enhanced or insufficient angiogenesis plays a role in some complications of diabetes including diabetic retinopathy or impaired wound healing, respectively [8]. In recent years, it is suggested that PPARs may be involved in regulating angiogenesis [9]; however,
%U http://www.hindawi.com/journals/ijpep/2012/637212/