Role of Peroxisome Proliferator-Activated Receptor Β Agonist on Angiogenesis in Hindlimb Ischemic Diabetic Rats Publisher Pubmed



Khazaei M¹ ; Salehi E¹ ; Rashidi B² ; Javanmard SH³ ; Fallahzadeh AR⁴
Source: Journal of Diabetes and its Complications Published:2012

Abstract

Introduction: 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 (55 mg/kg, ip). GW0742 was injected 1 day after surgery (1 mg/kg, sc). After 21 days, 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. Conclusion: PPARβ agonists restore skeletal muscle angiogenesis and can be considered for prevention and/or treatment of peripheral vascular complications in diabetic subjects. © 2012 Elsevier Inc. All rights reserved.