Noncoding RNAs in Vascular Cell Biology and Restenosis

SIMPLE SUMMARY: Angioplasty is a procedure where a stent is inserted to open a blocked blood vessel that is causing issues for a patient. Restenosis is a medical condition that reverses the benefits of angioplasty, and it is caused by injury from the stent, with inflammation, excessive smooth muscle cell growth and the movement of cells to accumulate inside the vessel, as part of a disproportionate healing response to the foreign object. The current treatments for restenosis stop the growth of all cells in the area, which is an issue as endothelial cells are required to keep growing in order to heal the inner layer of the blood vessel, which was damaged by the stent, and prevent issues in the future, such as blood clots. Noncoding RNAs are small pieces of genetic material that are not translated into proteins; however, they are important in controlling different biological processes, some of which are the growth and movement of specific cells involved in restenosis. Therefore, we may be able to target certain noncoding RNAs to only slow down the growth and movement of the type of cell causing the condition, namely smooth muscle cells, while allowing for endothelial cells to keep growing and healing the blood vessel. ABSTRACT: In-stent restenosis (ISR), characterised by ≥50% re-narrowing of the target vessel, is a common complication following stent implantation and remains a significant challenge to the long-term success of angioplasty procedures. Considering the global burden of cardiovascular diseases, improving angioplasty patient outcomes remains a key priority. Noncoding RNAs (ncRNAs) including microRNA (miRNA), long noncoding RNA (lncRNA) and circular RNA (circRNA) have been extensively implicated in vascular cell biology and ISR through multiple, both distinct and overlapping, mechanisms. Vascular smooth muscle cells, endothelial cells and macrophages constitute the main cell types involved in the multifactorial pathophysiology of ISR. The identification of critical regulators exemplified by ncRNAs in all these cell types and processes makes them an exciting therapeutic target in the field of restenosis. In this review, we will comprehensively explore the potential functions and underlying molecular mechanisms of ncRNAs in vascular cell biology in the context of restenosis, with an in-depth focus on vascular cell dysfunction during restenosis development and progression. We will also discuss the diagnostic biomarker and therapeutic target potential of ncRNAs in ISR. Finally, we will discuss the current shortcomings, challenges, and perspectives toward the clinical application of ncRNAs.