Similar Endothelial Glycocalyx Structures in Microvessels from a Range of Mammalian Tissues: Evidence for a Common Filtering Mechanism?

Abstract

The glycocalyx or endocapillary layer on the luminal surface of microvessels has a major role in the exclusion of macromolecules from the underlying endothelial cells. Current structural evidence in the capillaries of frog mesentery indicates a regularity in the structure of the glycocalyx, with a center-to-center fiber spacing of 20 nm and a fiber width of 12 nm, which might explain the observed macromolecular filtering properties. In this study, we used electron micrographs of tissues prepared using perfusion fixation and tannic acid treatment. The digitized images were analyzed using autocorrelation to find common spacings and to establish whether similar structures, hence mechanisms, are present in the microvessel glycocalyces of a variety of mammalian tissues. Continuous glycocalyx layers in mammalian microvessels of choroid, renal tubules, glomerulus, and psoas muscle all showed similar lateral spacings at ∼19.5 nm (possibly in a quasitetragonal lattice) and longer spacings above 100 nm. Individual glycocalyx tufts above fenestrations in the first three of these tissues and also in stomach fundus and jejunum showed evidence for similar short-range structural regularity, but with more disorder. The fiber diameter was estimated as 18.8 (± 0.2) nm, but we believe this is an overestimate because of the staining method used. The implications of these findings are discussed.

Fluid permeability of fibrous layers with finite thickness

“…Within the range of our analysis, such tendencies were commonly observed under different conditions of lx, ly, and lz. The case (iv) corresponds to the glycocalyx fiber structures observed experimentally [2]: a = 5 to 6 nm and lx = ly = lz = 20 nm, as mentioned above. Although the end effect in case (iv) may not seem so definite, the significant effect in cases (i) through (iii) suggests that the decrease in periodic spacing along the fibers (lz) or the increase in the perpendicular directions (lx, ly), possibly caused by the degeneration or suppression of the glycocalyx, may generate a considerable increase in permeation resistance near the surface of the glycocalyx layer.…”

“…Recent structural analyses have clarified the geometrical characteristics of the endothelial surface glycocalyx layer [2]. In the glycocalyx layer, core protein fibers with a diameter of 10 to 12 nm are aligned normal to the luminal wall and have a length, i.e., a layer thickness, of 150 to 400 nm, which varies among individuals as well as with the blood vessel site.…”

“…In the glycocalyx layer, core protein fibers with a diameter of 10 to 12 nm are aligned normal to the luminal wall and have a length, i.e., a layer thickness, of 150 to 400 nm, which varies among individuals as well as with the blood vessel site. There is a periodicity of approximately 20 nm in both directions along the fibers (spacing of core protein clusters) and parallel to the luminal wall (center-to-center distance of the fibers) [1,2]. Based on these observations, a mathematical model has been proposed.…”

“…Based on these observations, a mathematical model has been proposed. The structure of the endothelial surface glycocalyx layer is simplified in the model as parallel circular cylinders located regularly at the apexes of a square or hexagonal lattice [2]. However, such a cylinder model does not consider the effects of the periodic structure along the fibers and those of the finite layer thickness on the permeation characteristics, since the cylinders are assumed to be infinitely long.…”

Untangling the Knot in Diabetic Nephropathy: The Unanticipated Role of Glycocalyx in the Antiproteinuric Effect of Endothelin Receptor Antagonists

“…By in vitro studies, the authors demonstrated that incubation of human umbilical vein endothelial cells with plasma of patients with diabetes in flow condition decreased glycocalyx thickness and enhanced heparanase production. Although interesting, this finding should be confirmed in glomerular endothelial cells, in which the composition and thickness of the glycocalyx differ from that of the nonfenestrated endothelium (17). Boels at al.…”