Non-coding RNA in vascular pathophysiology (renewal)

Vascular injury, induced by divergent stimuli, leads to neointima formation, a process involving complex interplay between multiple cell types that naturally reside in the vessel wall and those that infiltrate vascular tissue post-injury. The resulting endothelial dysfunction, vascular smooth muscle cell phenotype switching and inflammation lead to neointima formation, a scenario that remains a major clinical burden. Our recent work has highlighted the importance of non-coding RNA, particularly miRNA, in post-injury neointima formation. In this application, we will define at the molecular, cellular and whole animal levels the connectivity between non-coding RNA and vascular cell regulation and function. We will focus on miRNA biogenesis, including assessment of main and passenger strands of the miRNA stem loop, regulation of miRNA clusters and detailed analysis of the target pathways affected by miRNA dysregulation, including vascular smooth muscle and endothelial components of the response to injury in novel murine genetic models. We will also integrate additional studies to evaluate the expression, regulation and function of long non-coding RNA (lncRNA). Collectively, our programme of work will provide a detailed fundamental understanding of the regulation and role of non-coding RNA in vascular neointima formation as well as provide innovative approaches for future translation to the clinic.