The role of m6A in vascular-related diseases: Regulatory mechanisms and therapeutic implications

Abstract

N⁶-methyladenosine (m⁶A) RNA modification is a critical regulator of gene expression in vascular-related diseases. By modulating RNA stability, splicing, and translation, m⁶A influences key processes such as endothelial function, vascular smooth muscle cell (VSMC) behavior, lipid metabolism and inflammation. m⁶A writers, erasers and readers dynamically regulate these processes, contributing to disease progression in conditions like atherosclerosis, aneurysms, hypertension and thrombosis. In atherosclerosis, m⁶A regulates lipid metabolism, foam cell formation, and inflammation, while influences VSMC apoptosis and extracellular matrix degradation in aneurysms. The role of m⁶A in vascular tension and thrombosis also makes it a promising target for therapeutic intervention. Emerging therapies aim to inhibit or enhance m⁶A methylation to control vascular remodeling, inflammation and endothelial dysfunction. RNA therapy based on m⁶A modification has the potential to promote angiogenesis and repair vascular damage. Despite the remarkable therapeutic promise of m⁶A, challenges remain in elucidating its tissue-specific and context-dependent roles. Future research should focus on advancing techniques for mapping m⁶A modifications and translating these findings into clinical applications, such as m⁶A-targeted therapeutics or biomarkers for early disease detection.