Epigenetic Regulation of the Vascular Endothelium by Angiogenic LncRNAs

The functional properties of the vascular endothelium are diverse and heterogeneous between vascular beds. This is especially evident when new blood vessels develop from a pre-existing closed cardiovascular system, a process termed angiogenesis. Endothelial cells are key drivers of angiogenesis as they undergo a highly choreographed cascade of events that has both exogenous (e.g., hypoxia and VEGF) and endogenous regulatory inputs. Not surprisingly, angiogenesis is critical in health and disease. Diverse therapeutics target proteins involved in coordinating angiogenesis with varying degrees of efficacy. It is of great interest that recent work on non-coding RNAs, especially long non-coding RNAs (lncRNAs), indicates that they are also important regulators of the gene expression paradigms that underpin this cellular cascade. The protean effects of lncRNAs are dependent, in part, on their subcellular localization. For instance, lncRNAs enriched in the nucleus can act as epigenetic modifiers of gene expression in the vascular endothelium. Of great interest to genetic disease, they are undergoing rapid evolution and show extensive inter- and intra-species heterogeneity. In this review, we describe endothelial-enriched lncRNAs that have robust effects in angiogenesis.