Testosterone and Voluntary Exercise Promote Angiogenesis in Hearts of Rats with Diabetes by Enhancing Expression of VEGF-A and SDF-1a

Objectives: Impaired angiogenesis in cardiac tissue is a major complication of diabetes. This study was aimed to evaluate the effects of testosterone and voluntary exercise on vascular endothelial growth factor-A (VEGF-A), stromal cell-derived factor 1a (SDF-1a) and myocardial capillary density in heart of rats with diabetes. Methods: Type 1 diabetes was induced by intraperitoneal injection of 55 mg/kg of streptozotocin in 80 male Wistar rats. After 42 days of treatment with testosterone (2 mg/kg/day) or voluntary exercise alone or in combination, angiogenesis was determined in the hearts by immunostaining for PECAM-1/CD31. The expressions of VEGF-A and SDF-1a levels in heart were also determined by the ELISA method. Results: Our results showed that capillary density, VEGF-A and SDF-1a levels in the heart were significantly decreased in castrated rats with diabetes, whereas these effects were reversed by testosterone and exercise. Furthermore, simultaneous treatment of castrated rats with diabetes with testosterone and exercise had a synergistic effect on capillary density, VEGF-A and SDF-1a levels in the heart. In the group with diabetes, either testosterone or exercise increased capillary density, VEGF-A and SDF-1a protein levels in heart tissue. However, the effects of combination therapy in rats with diabetes with testosterone and exercise on capillary density, VEGF-A and SDF-1a levels in the heart was synergistic. Conclusions: Our findings suggest that testosterone and exercise can promote neoangiogenesis in rats with diabetes and in castrated rats with diabetes. The proangiogenesis effect of testosterone and exercise is associated with the enhanced expression of VEGF-A and SDF-1a in heart tissue. (C) 2016 Canadian Diabetes Association.