Extracellular Vesicles as Epigenetic Regulators of Redox Homeostasis: A Systematic Review and Meta-Analysis.

Abstract

Extracellular vesicles (EVs) are emerging as key regulators of cellular communication, with increasing evidence supporting their role in oxidative stress (OS) modulation. In particular, the miRNA cargo of EVs plays a crucial role in mitigating OS and promoting redox balance through both direct antioxidant effects and epigenetic regulation. This study aimed to evaluate the impact of EVs on OS markers, influenced by their miRNA-mediated effects and potential epigenetic modifications in target cells. A systematic literature search was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines to identify studies reporting the effects of EVs on OS parameters. A meta-analysis was performed on key OS biomarkers, including reactive oxygen species (ROS), superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA). The heterogeneity of EV isolation and characterization techniques was also analyzed. The included studies demonstrated that EVs exert significant antioxidant effects by reducing ROS levels, increasing SOD activity and GSH levels, and lowering MDA levels. These effects were largely attributed to EV-miRNAs, which induce epigenetic modifications that modulate redox-related signaling pathways. However, the variability in EV isolation methods and characterization approaches highlights the need for standardization to improve data comparability. Despite their therapeutic potential, this significant heterogeneity in EV research remains a barrier to translation. Moreover, further exploration of epigenetic mechanisms is essential to fully harness their benefits for OS-related diseases.