The epitranscriptome: RNA modifications in vascular remodelling

RNA transcripts are not finished products. Like proteins undergo posttranslational modifications, RNAs undergo posttranscriptional modifications. Some of these modifications affect processing, stability or turnover of RNAs, others can 'edit' nucleotides, change the RNA's function and rewrite the genetic code. The body of RNA modifications is collectively called the 'epitranscriptome'. The epitranscriptome is dynamically regulated. This is the most clear for N6-methyladenosine (m6A), where both m6A-'writers' and -'erasers' have been identified and are also already being employed in studies on the effects of broad-scale m6A modifications on human disease, including cardiovascular disease. Even though not all modifications are readily reversible like m6A, most, if not all, other modifications are actively regulated in response to stressors, such as ischemia, starvation, or incubation with for example cytokines or oxidized LDL, all important factors in vascular remodelling and cardiovascular disease. Epitranscriptome research in human disease in general and in cardiovascular research is still in its infancy and methods to reliably detect and/or manipulate most RNA modifications are still lacking. Nonetheless, the number of studies on RNA modification and on writer-, eraser-, and reader-protein in various forms of vascular remodelling has increased dramatically over the last three years. This review aimed to discuss the available literature on the most common RNA modifications in different forms of vascular remodelling. Both adaptive vascular remodelling, including postischemic angiogenesis, as well as maladaptive remodelling, like atherosclerosis and aneurysm formation, and their direct consequences, such as myocardial infarction, acute stroke, peripheral artery disease and abdominal aorta aneurysm, have been discussed.