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Decreased Cardiac NOX4 and SIRT-1 Protein Levels Contribute to Decreased Angiogenesis in the Heart of Diabetic Rats:
Shiva Roshan Milani1,2, Bagher Pourheydar3,2, Saman Daneshfar4
1Department of Physiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran.
Insights
Diabetes reduces heart angiogenesis by decreasing NOX4 and SIRT-1. Insulin-like growth factor 1 (IGF-1) and exercise therapy restored these levels, improving heart health in diabetic rats.
Area of Science:
- Cardiovascular Research
- Metabolic Disease Research
- Molecular Biology
Background:
- Reduced heart angiogenesis is a key risk factor for heart disease in diabetes.
- NADPH oxidase 4 (NOX4) and sirtuin 1 (SIRT-1) are critical angiogenesis mediators.
- Understanding their role in diabetic cardiomyopathy is crucial for therapeutic development.
Purpose of the Study:
- To investigate changes in NOX4 and SIRT-1 protein levels in the hearts of diabetic rats.
- To evaluate the impact of Insulin-like Growth Factor 1 (IGF-1) and exercise on these mediators.
- To assess the combined effect of IGF-1 and exercise on angiogenesis in diabetic hearts.
Main Methods:
- Type 1 diabetes was induced in male Wistar rats using streptozotocin.
- Angiogenesis was assessed via PECAM-1/CD31 immunostaining.
- NOX4 and SIRT-1 expression levels were quantified using ELISA.
Main Results:
- Diabetic rats showed increased HbA1c, decreased SIRT-1, NOX4 levels, and reduced angiogenesis.
- IGF-1 and exercise interventions, individually or combined, reversed these diabetes-induced changes.
- A synergistic effect was observed for IGF-1 and exercise on SIRT-1, HbA1c, and angiogenesis.
Conclusions:
- Downregulation of NOX4 and SIRT-1 protein levels may mediate reduced cardiac angiogenesis in diabetes.
- IGF-1 and exercise represent potential therapeutic strategies to increase NOX4 and SIRT-1 levels in diabetic rat hearts.
- Combined IGF-1 and exercise therapy demonstrates a potent synergistic effect for improving cardiac angiogenesis in diabetes.
Abstract:
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, NADPH oxidase 4 (NOX4) and sirtuin 1 (SIRT-1) protein levels in the heart of diabetic rats and the impact of Insulin-like growth factor 1 (IGF-1) and exercise on these proteins. Injection of 60 mg/kg of streptozotocin 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. The results revealed a significant increase in HbA1c and a significant decrease in SIRT1, 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. 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.
