MicroRNAs Regulating Reactive Oxygen Species in Cardiovascular Diseases

Significance: Oxidative stress caused by overproduction of reactive oxygen species (ROS) in cells is one of the most important contributors to the pathogenesis of cardiovascular and metabolic diseases such as hypertension and atherosclerosis. Excessive accumulation of ROS impairs, while limiting oxidative stress protects cardiovascular and metabolic function through various cellular mechanisms. Recent Advances: MicroRNAs (miRNAs) are novel regulators of oxidative stress in cardiovascular cells that modulate the expression of redox-related genes. This article summarizes recent advances in our understanding of how miRNAs target major ROS generators, antioxidant signaling pathways, and effectors in cells of the cardiovascular system. Critical Issues: The role of miRNAs in regulating ROS in cardiovascular cells is complicated because miRNAs can target multiple redox-related genes, act on redox regulatory pathways indirectly, and display context-dependent pro- or antioxidant effects. The complex regulatory network of ROS and the plethora of targets make it difficult to pin point the role of miRNAs and develop them as therapeutics. Therefore, these properties should be considered when designing strategies for therapeutic or diagnostic development. Future Directions: Future studies can gain a better understanding of redox-related miRNAs by investigating their own regulatory mechanisms and the dual role of ROS in the cardiovascular systems. The combination of improved study design and technical advancements will reveal newer pathophysiological importance of redox-related miRNAs. Antioxid. Redox Signal. 00, 000-000.