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

Abstract

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.

Deletion of murine slc29a4 modifies vascular responses to adenosine and 5‐hydroxytryptamine in a sexually dimorphic manner

“…The ENT4 substrates adenosine and 5‐HT are prominent among these endogenous regulators. Dynamic regulation of local blood flow is generally attributed to vascular endothelial mechanisms, specifically NOS generated NO and K Ca channel‐mediated endothelial hyperpolarization (EDH; Kerr et al, 2012; Khaddaj Mallat, 2017). Thus, we assessed the relative contribution of NO and EDH mechanisms to the responses of isolated mesenteric arteries to the vascular regulators acetylcholine/methacholine, adenosine, and 5‐HT in both male and female WT and ENT4‐KO mice.…”

Type 2 Diabetes Alters Intracellular Ca2+ Handling in Native Endothelium of Excised Rat Aorta

“…Moreover, sprouting angiogenesis, which drives the formation of new capillaries from pre-existing microvessels, is exacerbated in the retina, thereby resulting in retinopathy [9].An increase in intracellular Ca 2+ concentration ([Ca 2+ ] i ) is crucial to fine tune endothelial cell functions [10][11][12]. For instance, endothelial Ca 2+ signals drive the release of many vasodilators, including nitric oxide, prostacyclin, arachidonic acid metabolites and hydrogen sulfide, and recruit Ca 2+ -activated K + channels to stimulate endothelium-dependent hyperpolarization [13][14][15][16]. In addition, an increase in endothelial [Ca 2+ ] i leads to the production of the vasoconstrictor prostanoids, thromboxane A2, prostaglandin H2 and endothelin-1 [14,17,18].…”

“…In addition, an increase in endothelial [Ca 2+ ] i leads to the production of the vasoconstrictor prostanoids, thromboxane A2, prostaglandin H2 and endothelin-1 [14,17,18]. Vasoactive agonists bind to specific G-protein coupled receptors to engage phospholipase Cβ, a membrane-bound enzyme that cleaves inositol-1,4,5-trisphosphate (InsP 3 ) from its precursor phosphatidylinositol-4,5-bisphosphate [14,15]. The following Ca 2+ response typically consists of an initial Ca 2+ peak, which is mediated by InsP 3 -induced Ca 2+ release from the endoplasmic reticulum (ER), followed by a prolonged influx of Ca 2+ , known as a plateau [19,20].…”

Effects of hydrogen sulphide on oxidative stress, inflammatory cytokines, and vascular remodelling in l‐NAME‐induced hypertension

“…Hypertension is a common health problem with a complicated pathophysiology. Recently it was found that the positive feedback loop comprising oxidative stress, inflammation, and endothelial dysfunction may play a key role in the pathogenesis and progression of hypertension . The cross‐talk between NO and H 2 S represents a promising field of research and has attracted a great deal of interest recently as the defect in NO/H 2 S homeostasis is involved in the pathogenesis of hypertension and has a strong influence on vascular tone regulation .…”

“…Hypertension is a substantial health problem that results in cardiovascular remodelling and serious complications such as stroke and ischaemic heart disease . The pathophysiology of hypertension is very complicated and recent evidence suggests that the positive feedback loop comprising oxidative stress, inflammation, and endothelial dysfunction may play a crucial role in the pathogenesis and progression of hypertension …”