Micro RNA-126 promoting angiogenesis in diabetic heart by VEGF/Spred-1/Raf-1 pathway: effects of high-intensity interval training

J Diabetes Metab Disord. 2020 Aug 8;19(2):1089-1096. doi: 10.1007/s40200-020-00610-4. eCollection 2020 Dec.

Abstract

Purpose: This study aims to investigate the effect of high-intensity interval training (HIIT) on gene expression of MicroRNA-126 (miR-126) and serum concentration of vascular endothelial growth factor/ sprouty related EVH1 domain containing 1/ rapidly accelerated fibrosarcoma 1 (VEGF/Spred-1/Raf-1) proteins effective in cardiac tissue angiogenesis of diabetic rats.

Methods: Forty male Wistar rats were randomly divided into four groups of healthy control (HC), diabetic control (DC), diabetic with HIIT training (DT), and healthy with HIIT training (HT). HIIT was performed 6 days per week for 6 weeks (with the overload). Diabetes was induced via the combination of intraperitoneal injection of streptozotocin and high-fat foods.

Results: Diabetes remarkably diminished the expressions of miR-126, VEGF and Raf-1 proteins, and augmented Spred-1 expression. Meanwhile, the implementation of HIIT gave rise to a significant enhancement in expression of miR-126 heart tissue (P < 0.01), and subsequently increased the expression of VEGF and Raf-1 proteins (P < 0.01), and declined Spred-1 expression (P < 0.01) in the training group compared to the control group.

Conclusion: The results of this study show that HIIT increases the expression of miR-126 by activating the angiogenesis pathway of the heart tissue. Increased angiogenesis through the miR-126 pathway is vital to compensate for heart destruction induced by diabetes. Thus, the use of standard interval exercise can be introduced as a novel therapeutic target for diabetic cardiomyopathy.

Keywords: Diabetes mellitus; Exercise; Heart muscle; VEGF; miR-126.