Voluntary wheel running and testosterone replacement increases heart angiogenesis through miR-132 in castrated diabetic rats

Objective: Low levels of testosterone in men with diabetes are associated with cardiovascular complications. We investigated the effect of testosterone and voluntary exercise on heart angiogenesis in castrated diabetic rats. Methods: Sixty-three diabetic rats were treated with testosterone 2 mg/kg/day or voluntary exercise alone or combination of these two for 6 weeks. At the end of the study, heart tissue samples were collected and used for CD31 detection by immunohistochemical method and determination of miR-132 levels. Results: miR-132 levels and CD31 of heart tissue were higher after testosterone administration and in the voluntary exercise group in diabetic rats after 6 weeks. Combination of testosterone and voluntary exercise had synergistic effect on angiogenesis and miR-132 level. In castrated diabetic rats, there were significantly lower levels of miR-132 and CD31 in heart tissue compared to the diabetic group, whereas testosterone and exercise reversed these effects. In addition, testosterone supplementation plus exercise had an additive effect on miR-132 levels and CD31 in castrated diabetic rats. Conclusions: It was concluded that castration in rats leads to reduced miR-132 levels and subsequently decreased angiogenesis in diabetes. Testosterone plus voluntary exercise improved angiogenesis possibly through enhancement of miR-132 levels in heart of castrated diabetic rats.