The vascular endothelium: A regulator of arterial tone and interface for the immune system

As the primary interface between the blood and various tissues of the body, the vascular endothelium exhibits a diverse range of roles and activities, all of which contribute to the overall health and function of the cardiovascular system. In this focused review, we discuss several key aspects of endothelial function, how this may be compromised and subsequent consequences. Specifically, we examine the dynamic regulation of arterial contractility and distribution of blood flow through the generation of chemical and electrical signaling events that impinge upon vascular smooth muscle. The endothelium can generate a diverse range of vasoactive compounds and signals, most of which act locally to adjust blood flow in a dynamic fashion to match tissue metabolism. Disruption of these vascular signaling processes (e.g. reduced nitric oxide bioavailability) is typically referred to as endothelial dysfunction, which is a recognized risk factor for cardiovascular disease in patients and occurs early in the development and progression of hypertension, atherosclerosis and tissue ischemia. Endothelial dysfunction is also associated with type-2 Diabetes and aging and increased mechanistic knowledge of the cellular changes contributing to these effects may provide important clues for interventional strategies. The endothelium also serves as the initial site of interaction for immune cells entering tissues in response to damage and acts to facilitate the actions of both the innate and acquired immune systems to interact with the vascular wall. In addition to representing the main cell type responsible for the formation of new blood vessels (i.e. angiogenesis) within the vasculature, the endothelium is also emerging as a source of extracellular vesicle or microparticles for the transport of signaling molecules and other cellular materials to nearby, or remote, sites in the body. The characteristics of released microparticles appear to change with the functional status of the endothelium; thus, these microparticles may represent novel biomarkers of endothelial health and more serious cardiovascular disease.