The vascular endothelium is comprised of a single cell-thick layer of endothelial cells (EC) that line blood vessels and lymphatic vessels. Its physical strength is provided by tight junctions, adherens junctions, and focal adhesions between adjacent EC. Intercellular adhesions also support the barrier function of the endothelium by restricting the passage of ions and larger molecules between the apical and basolateral sides. Endothelial cells mediate the uptake of circulating nutrients and are responsive to endocrine hormones, angiogenic factors, and neurotransmitters. In addition, endothelial production of the vasorelaxant nitric oxide is critical for the maintenance of vascular tone.
EC express innate immune receptors which trigger the secretion of inflammatory mediators and the upregulation of leukocyte adhesion proteins. Leukocytes can adhere to the activated epithelium and migrate between endothelial cells to reach sites of inflammation. Integrity of the endothelial barrier is maintained by the regulated detachment and reassociation of intercellular EC junctions as leukocytes pass through. The vascular endothelium becomes dysfunctional following injury or in chronic inflammatory diseases such as atherosclerosis, diabetes, and cancer. In these settings, EC exhibit dysregulated transendothelial permeability, production of vasorelaxant factors, and intracellular signaling.