N6-methyladenosine (m6A) post-transcriptional modification regulation of mRNA, an overlooked therapeutic opportunity to leverage mRNA processing in vascular smooth muscle cells.

In response to pathological stimuli, VSMCs modulate from a quiescent, contractile phenotype to a synthetic, non-contractile phenotype with increased migration, proliferation, and expression of matrix and pro-inflammatory cytokines. This response necessitates modification in expression of a plethora of mRNA transcripts, which often requires fine-tuning by post-translational changes in the stability of these mRNAs. N6-methyladenosine (m6A) modification can affect the fate of many mRNA transcripts in the cell, especially mRNA stability. Various m6A regulatory proteins, such as writers (methylases), erasers (demethylases), and readers (RNA binding proteins) are involved in various homeostatic processes in the cell, and can become dysregulated in disease states, contributing to vascular pathology. Recently, it has been shown that these m6A modulatory proteins can be targeted therapeutically with small molecule inhibitors to alter their expression and activity in the cell, opening up the possibility that targeting modifiers of the mRNA methylome can be leveraged as a therapeutic opportunity to treat vascular diseases. This review describes the mechanisms and explores roles of m6A modification in mRNA processing and how these changes in the VSMC transcriptome can contribute to pathogenesis and possibly treatment of vascular diseases.