The vascular endothelium and human diseases

Abstract

Alterations of endothelial cells and the vasculature play a central role in the pathogenesis of a broad spectrum of the most dreadful of human diseases, as endothelial cells have the key function of participating in the maintenance of patent and functional capillaries. The endothelium is directly involved in peripheral vascular disease, stroke, heart disease, diabetes, insulin resistance, chronic kidney failure, tumor growth, metastasis, venous thrombosis, and severe viral infectious diseases. Dysfunction of the vascular endothelium is thus a hallmark of human diseases. In this review the main endothelial abnormalities found in various human diseases such as cancer, diabetes mellitus, atherosclerosis, and viral infections are addressed.

Keywords: Atherosclerosis; Cancer.; Endothelial dysfunction; Endothelium; Stroke.

Fig 1

The healthy endothelium not only arbitrates endothelium-dependent vasodilation, but also actively suppresses thrombosis, vascular inflammation, and hypertrophy. This schematic depicts differences between a healthy endothelium (A) and a dysfunctional one (B). A healthy endothelium displays a vasodilatory phenotype consisting of high levels of vasodilators such as nitric oxide (NO) and prostacyclin (PGI₂) and low levels of reactive oxygen species (ROS) and uric acid. A healthy endothelium also has an anticoagulative phenotype consisting of low levels of plasminogen activator inhibitor 1 (PAI-1), von Willebrand factor (vWF), and P-selectin. Very little inflammation may be present, as indicated by low levels of soluble vascular cell adhesion molecule (sVCAM.), soluble intercellular adhesion molecule (sICAM), E-selectin, C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6). Finally, the population of endothelial progenitor cells (EPCs, indicative of vascular repair capacity) is high; whereas levels of endothelial microparticles (EMPs) and circulating endothelial cells (CECs), indicative of endothelial stress/damage, are low. In the case of a dysfunctional endothelium, the phenotypic characteristics include impaired vasodilation, increased oxidative stress/uric acid, lipid peroxide radical,Nitrotyrosine and Nitirc oxide, and a procoagulant and pro-inflammatory phenotype with decreased vascular repair capacity and increased numbers of EMPs and CECs. 6-keto PGF1α: 6 keto prostaglandin F1-alpha, a stable product of PGI₂; ADMA; asymmetric dimethyl arginine, inhibitor of NO biosynthesis; EC: endothelial cell; NO₂^-: nitrite ion, stable degradation product of NO; NO₃^- nitrate ion, stable degradation product of NO; ONOO^-: peroxynitrite, the product of superoxide-mediated inactivation of NO; VSMC: vascular smooth muscle cell; WBC: white blood cell. (Modified from Dylan Burger and Rhian MT 2012).

Fig 2

Schematic representation of endothelial dysfunction on human diseases.