Abstract
There is increasing evidence that peroxisome proliferator-activated receptors (PPARs) may be involved in the regulation of angiogenesis. In this study, we examined whether rosiglitazone, a PPARγ agonist, can restore angiogenesis in a rat hindlimb ischemia model of diabetes. Male wistar rats were divided into four groups (n=6 each): control, diabetic and control and diabetic rats who received rosiglitazone (8 mg/kg/day). Diabetes was induced by streptozotocin (55 mg/kg; ip). After 21 days, serum concentrations of nitric oxide (NO), vascular endothelial growth factor (VEGF) and soluble VEGF receptor-2 (VEGFR-2) were measured and neovascularization in ischemic legs was evaluated by immunohistochemistry. Capillary density and capillary/fiber ratio in hindlimb ischemia of diabetic animals were significantly lower than the control group (P<0.05). Rosiglitazone significantly restored neovascularization in diabetic animals (P<0.05). rosiglitazone enhances neovascularization in diabetic ischemic skeletal muscle and could be considered for treatment of peripheral artery disease in diabetic subjects.
Highlights
Type 2 diabetes is a major cause of morbidity and mortality in advanced societies
Blood samples were centrifuged with 10000 rpm for 15 min to obtain serum triglycerides (TG), High-density lipoprotein cholesterol (HDL-C), Total cholesterol (TC) and Lowdensity lipoprotein cholesterol (LDL-C), glucose and insulin concentrations with commercially available kits
We investigated the role of rosiglitazone, a PPARγ agonist, on angiogenesis in hindlimb ischemia in diabetic and control rats
Summary
Type 2 diabetes is a major cause of morbidity and mortality in advanced societies. Cardiovascular disease is responsible for up to 80% of death in diabetic subjects[1]. Some of the long-term complications of diabetes are associated with impaired angiogenesis which can result in severe organ damage[2]. Angiogenesis is defined as sprouting of blood vessels from preexisting ones and is considered a physiological response to tissue ischemia[3,4]. We examined whether rosiglitazone, a PPARγ agonist, can restore angiogenesis in a rat hindlimb ischemia model of diabetes. Male wistar rats were divided into four groups (n=6 each): control, diabetic and control and diabetic rats who received rosiglitazone (8 mg/kg/day). Capillary density and capillary/fiber ratio in hindlimb ischemia of diabetic animals were significantly lower than the control group (P
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