Glycocalyx and sepsis-induced alterations in vascular permeability

Abstract

Endothelial cells line the inner portion of the heart, blood vessels, and lymphatic vessels; a basal membrane of extracellular matrix lines the extraluminal side of endothelial cells. The apical side of endothelial cells is the site for the glycocalyx, which is a complex network of macromolecules, including cell-bound proteoglycans and sialoproteins. Sepsis-associated alterations of this structure may compromise endothelial permeability with associated interstitial fluid shift and generalized edema. Indeed, in sepsis, the glycocalyx acts as a target for inflammatory mediators and leukocytes, and its ubiquitous nature explains the damage of tissues that occurs distant from the original site of infection. Inflammatory-mediated injury to glycocalyx can be responsible for a number of specific clinical effects of sepsis, including acute kidney injury, respiratory failure, and hepatic dysfunction. Moreover, some markers of glycocalyx degradation, such as circulating levels of syndecan or selectins, may be used as markers of endothelial dysfunction and sepsis severity. Although a great deal of experimental evidence shows that alteration of glycocalyx is widely involved in endothelial damage caused by sepsis, therapeutic strategies aiming at preserving its integrity did not significantly improve the outcome of these patients.

Figure 1

Glycocalyx structure and the glycocalyx-endothelial barrier. ATIII, anti thrombin III; GAG, glycosaminoglycan.

Figure 2

Glycocalyx characteristics in normal endothelium (left) and during endothelial dysfunction (right). ETC, endothelial cleft.

Figure 3

Modification of glycocalyx components during sepsis. Representative light microphotograph of MAA (Maackia amurensis agglutinin) lectin histochemistry in mesoceacum of sham-operated (on the left side) and CLP (cecal ligation and puncture)-treated rats (on the right side) at 7 hours after surgery. In blue, MAA reactivity (indicating the presence of sialic acid linked α2,3 to galactose, arrows) was intense in mesoceacal vessels of sham operated rats (left side) and reduced in vessels of CPL rats (right side). Scale bar = 25 μm. Courtesy of Eleonora Sgambati.