All cells – from single-cell microorganisms to highly organized mammalian cells – are shielded from their surrounding milieu by a membranous, carbohydrate-rich layer, or glycocalyx. The glycocalyx also is involved in nutrient uptake, and it facilitates the binding and concentrating of factors necessary for proper cell function. In the vasculature, the endothelial glycocalyx protects the vascular wall from direct exposure to flowing blood, contributes to the vascular permeability barrier and its antiadhesive properties, and stimulates the endothelial release of nitric oxide in response to fluid shear stress.

Historically, studies aimed at understanding mechanisms of endothelial permeability led to the concept that vessel walls are lined with an extracellular layer of membrane-bound substances (1,2). Danielli (1), and Chambers and Zweifach (2) hypothesized the existence of a thin, noncellular layer on the endothelial surface, termed the endocapillary layer. In the latter study, the perfusion of frog mesentery with an Evans blue–containing solution revealed blue-colored thin strands and sheets of translucent material on the inner surface of the capillary (2). In subsequent experiments involving intravenous injections of pontamine sky blue and intravital microscopy of the hamster cheek pouch, Copley and Staple observed an unstained plasmatic zone adjacent to the endothelial surface, giving rise to the notion that the endothelial surface is covered by a thin molecular layer (the endoendothelial fibrin lining) and an adjacent immobile plasma region (3).

To date, although both concepts, in essence, still hold true, novel data on the structural and compositional properties of the endothelial glycocalyx implicate a highly active role for this noncellular layer in vascular wall homeostasis.