121 - Introductory Essay: The Endothelium in Health and Disease

Summary

The endothelium is an expansive organ, reaching to all recesses of the human body. The endothelium plays a critical role in homeostasis. Endothelial cells (ECs) participate in the regulation of vasomotor tone, leukocyte trafficking, coagulation, permeability, antigen presentation, innate immunity, and angiogenesis. ECs display remarkable heterogeneity in structure and function. For example, although most ECs are extremely flat (which minimizes diffusional path length), those of the high endothelial venules (HEVs) are plump and cuboidal. The structure of the intercellular junctions, the absence or presence of fenestrations, and the continuity (or lack thereof) of the abluminal basement membrane are criteria used to differentiate between continuous, fenestrated, and sinusoidal endothelium. The ECs in postcapillary venules are primarily responsible for mediating the adhesion and transmigration of leukocytes, whereas arteriolar endothelium plays a particularly important role in regulating vasomotor tone. ECs are aligned parallel to the direction of blood flow in straight segments of arteries, but not at branch points or curvatures of arteries, or in veins. Protein and mRNA expression varies among different vascular beds. Indeed, state-of-the-art proteomic approaches have uncovered a vast array of vascular bed-specific markers, or vascular “zip codes.”

EC heterogeneity is mediated by two proximate (“how?”) mechanisms. First, biochemical and biomechanical signals within the extracellular environment trigger posttranscriptional and/or post-translational changes in ECs. Because the net signal input varies across the vascular tree (and from one moment to the next), so too does EC output (i.e., cellular phenotype). Second, certain site-specific properties of the endothelium are epigenetically programmed and mitotically heritable. The maintenance of these latter properties are no longer dependent on or influenced by the extracellular milieu.