Non-coding RNAs in endothelial cell signalling and hypoxia during cardiac regeneration.

Heart failure (HF) as a result of myocardial infarction (MI) is the leading cause of death worldwide. In contrast to the adult mammalian heart, which has low regenerative capacity, newborn mammalian and zebrafish hearts can completely regenerate after injury. Cardiac regeneration is considered to be mediated by proliferation of pre-existing cardiomyocytes (CMs) mainly located in a hypoxic niche. To find new therapies to treat HF, efforts are being made to understand the molecular pathways underlying the regenerative capacity of the heart. However, the multicellularity of the heart is important during cardiac regeneration as not only CM proliferation but also the restoration of the endothelium is imperative to prevent progression to HF. It has recently come to light that signalling from non-coding RNAs (ncRNAs) and extracellular vesicles (EVs) plays a role in the healthy and the diseased heart. Multiple studies identified differentially expressed ncRNAs after MI, making them potential therapeutic targets. In this review, we highlight the molecular interactions between endothelial cells (ECs) and CMs in cardiac regeneration and when the heart loses its regenerative capacity. We specifically emphasize the role of ncRNAs and cell-cell communication via EVs during cardiac regeneration and neovascularisation.