title: Role of peroxisome proliferator-activated receptor β agonist on angiogenesis in hindlimb ischemic diabetic rats.
abstract: BACKGROUND
  Studies indicated that PPARβ agonists play a role in modulation of angiogenesis. In this study, we evaluated the effect of specific PPARβ agonist, GW0742, on angiogenesis and serum vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2), and nitrite concentrations in hindlimb ischemia in normal and diabetic rats.
  
  
  METHODS
  Hindlimb ischemic rats were divided into four groups: control, diabetic, control, and diabetic treated with GW0742 (n=7 each). Diabetes was induced by injection of streptozotocin (55mg/kg, ip). GW0742 was injected 1day after surgery (1mg/kg, sc). After 21days, blood samples were taken, and gastrocnemius muscles were harvested for immunohistochemistry.
  
  
  RESULTS
  GW0742 significantly increased serum nitrite and VEGFR-2 concentrations and VEGF-to-VEGFR-2 ratio in control and diabetic rats. Capillary density was lower in diabetic animals compared to the control, and GW0742 significantly restored the capillary density in the control and diabetic hindlimb ischemic rats.
  
  
  CONCLUSIONS
  PPARβ agonists restore skeletal muscle angiogenesis and can be considered for prevention and/or treatment of peripheral vascular complications in diabetic subjects.
authors.affiliation: Department of Physiology, Isfahan University of Medical Sciences, Isfahan, Iran. Khazaei@med.mui.ac.ir
authors.forename: M
authors.initials: M
authors.lastname: Khazaei
authors.forename: E
authors.initials: E
authors.lastname: Salehi
authors.forename: B
authors.initials: B
authors.lastname: Rashidi
authors.forename: S H
authors.initials: SH
authors.lastname: Javanmard
authors.forename: A R
authors.initials: AR
authors.lastname: Fallahzadeh
mesh_terms: D000818:Animals; D002196:Capillaries / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D017719:Diabetic Foot / Q000188:drug therapy* / Q000503:physiopathology; D006614:Hindlimb / Q000098:blood supply*; D007511:Ischemia / Q000188:drug therapy*; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009573:Nitrites / Q000097:blood; D048068:PPAR-beta / Q000819:agonists*; D051381:Rats; D017208:Rats, Wistar; D013844:Thiazoles / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000097:blood; D010636:Phenols; D013438:Sulfhydryl Compounds
chemical_list: D009573:Nitrites; D048068:PPAR-beta; D013844:Thiazoles; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; C467498:vascular endothelial growth factor A, rat; C479979:(4-(((2-(3-fluoro-4-(trifluoromethyl)phenyl)-4-methyl-1,3-thiazol-5-yl)methyl)sulfanyl)-2-methylphenoxy)acetic acid; D010636:Phenols; D013438:Sulfhydryl Compounds