Decreased Cardiac NOX4 and SIRT-1 Protein Levels Contribute to Decreased Angiogenesis in the Heart of Diabetic Rats: Rescue Effects of IGF-I and Exercise

Abstract

Purpose: Reduced angiogenesis in the heart tissue is a primary risk factor for heart disease in the diabetes condition. This study was aimed to evaluate the changes of two main angiogenesis mediators, NOX4 and SIRT-1 protein levels in the heart of diabetic rats and the impact of IGF-I and exercise on these proteins. Methods: Injection of 60 mg/kg of streptozoctin in 40 male Wistar rats led to the induction of type 1 diabetes. Angiogenesis was detected in the hearts by immunostaining for PECAM-1/CD31 after 30 days of treatment with IGF-1 (2 mg/kg/day) and exercise. ELISA technique was utilized to establish the expression levels of NOX4 and SIRT-1 within the heart. Results: The results revealed a significant increase in HbA1c and a significant decrease in SIRT-1, NOX4 levels and angiogenesis grade in the heart of diabetes group compared to control group. Meanwhile, IGF-1 and exercise alone or in combination completely masked these effects. Additionally, synergistic effect on SIRT-1, HbA1c levels and angiogenesis grade is evident when IGF-1 and exercise are applied simultaneously. Conclusions: Our findings suggest that reduction in angiogenesis in the heart of diabetic rats may be mediated by down expression of NOX4 and SIRT-1 protein levels. It was also displayed that IGF-1 and exercise as novel therapies increase NOX4 and SIRT-1 protein levels within the hearts of diabetic rats.