Role of peroxisome proliferator-activated receptor β agonist on angiogenesis in hindlimb ischemic diabetic rats

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...

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Published in:Journal of diabetes and its complications 2012-03, Vol.26 (2), p.137-140
Main Authors: Khazaei, M, Salehi, E, Rashidi, B, Javanmard, S.H, Fallahzadeh, A.R
Format: Article
Language:English
Subjects:
Angiogenesis
Animals
Capillaries - drug effects
Diabetes
Diabetes Mellitus, Experimental - complications
Diabetic Foot - drug therapy
Diabetic Foot - physiopathology
Endocrinology & Metabolism
Hindlimb - blood supply
Ischemia - drug therapy
Male
Muscle, Skeletal - blood supply
Muscle, Skeletal - drug effects
Neovascularization, Physiologic - drug effects
Nitric oxide
Nitrites - blood
PPAR
PPAR-beta - agonists
Rats
Rats, Wistar
Thiazoles - pharmacology
Vascular Endothelial Growth Factor A - blood
Vascular Endothelial Growth Factor Receptor-2 - blood
VEGF
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Summary: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.
ISSN:1056-8727
1873-460X
DOI:10.1016/j.jdiacomp.2012.02.005