ET block and the neointima: not the B, that is the answer

This editorial refers to ‘Non-endothelial cell endothelin-B receptors limit neointima formation following vascular injury’ by N. S. Kirkby et al ., pp. 19–28, this issue. The walls of blood vessels are a hive of activity. Components, including the endothelium, internal elastic lamina, smooth muscle cells (SMCs) of the media, and the adventia with its nerves, are all involved in a complexity of interacting functions. These include, but are not limited to, regulation of blood pressure and tissue perfusion, mechanosensation of flow and stretch, release of various relaxing and contracting factors, and modulation of inflammatory processes. Significant two-way communication between the main players, the endothelium and SMC, involves paracrine factors and hormonal signalling but can also involve direct physical contact and electrical and chemical continuity via myoendothelial gap junctions (MEGJs).1 Additional signalling can arise from sympathetic and sensory nerves.2 Compounding the situation can be various pathologies that include inflammatory processes involving leucocytes and macrophages and release of cytokines and various growth factors.3 Perhaps not surprisingly, SMCs exposed to such an environment can go walkabout. Compelling evidence indicates that SMCs have a highly plastic phenotype. Although they normally take the form of differentiated, contractile cells, changes in the environmental milieu, such as from injury, can switch the cells to a range of phenotypes that can include migrating de-differentiated cells with a synthetic and proliferative phenotype, macrophage-like, foam-like, phagocytic-like,4–7 and chondrocyte-like cells.8 Many of these effects are mediated intracellularly by a host of microRNAs interacting with a multitude of cellular messenger …