Reactive Oxygen Species-Mediated Diabetic Heart Disease: Mechanisms and Therapies

Significance: Diabetic heart disease (DHD) is the primary cause of mortality in people with diabetes. A significant contributor to the development of DHD is the disruption of redox balance due to reactive oxygen species (ROS) overproduction resulting from sustained high glucose levels. Therapies specifically focusing on the suppression of ROS will hugely benefit patients with DHD. Recent Advances: In addition to the gold standard pharmacological therapies, the recent development of gene therapy provides an exciting avenue for developing new therapeutics to treat ROS-mediated DHD. In particular, microRNAs (miRNAs) are gaining interest due to their crucial role in several physiological and pathological processes, including DHD. Critical Issues: miRNAs have many targets and differential function depending on the environment. Therefore, a proper understanding of the function of miRNAs in specific cell types and cell states is required for the successful application of this technology. In the present review, we first provide an overview of the role of ROS in contributing to DHD and the currently available treatments. We then discuss the newer gene therapies with a specific focus on the role of miRNAs as the causative factors and therapeutic targets to combat ROS-mediated DHD. Future Directions: The future of miRNA therapeutics in tackling ROS-mediated DHD is dependent on a complete understanding of how miRNAs behave in different cells and environments. Future research should also aim to develop conditional miRNA therapeutic platforms capable of switching on and off in response to disruptions in the redox state. Antioxid. Redox Signal. 36, 608-630.