Glycocalyx: a new diagnostic and therapeutic target in sepsis

Abstract

The glycocalyx is a gel-like layer covering the luminal surface of vascular endothelial cells. It is comprised of membrane-attached proteoglycans, glycosaminoglycan chains, glycoproteins, and adherent plasma proteins. Glycocalyx maintains homeostasis of the vascular network: controls vascular permeability and microvascular tone, prevents microvascular thrombosis and regulates leukocyte adhesion. During sepsis, the glycocalyx is degraded via inflammatory mechanisms such as metalloproteinases, heparanases and hyaluronidases. These sheddases are activated by the reactive oxygen species and pro-inflammatory cytokines, such as tumour necrosis factor alpha and interleukin-1beta. Inflammation-mediated glycocalyx degradation leads to vascular hyperpermeability, unregulated vasodilation, microvascular thrombosis, and augmented leukocyte adhesion. Clinical studies have demonstrated a correlation between blood levels of the glycocalyx components with organ dysfunction, severity and mortality in sepsis. Fluid resuscitation therapy is an essential part of the sepsis treatment, but overaggressive fluid therapy practices (that lead to hypervolemia) can increase the destruction of glycocalyx. Conversely, fresh frozen plasma and albumin administration can attenuate glycocalyx degradation. The beneficial and detrimental effects of the infusion of solutions and plasma on glycocalyx integrity in sepsis are not well understood; further research will be conducted. This review (1) analyzes the main mechanisms of glycocalyx destruction in sepsis; (2) demonstrates the relation of the blood and urine levels of glycocalyx components with the results of patient treatment; (3) shows the beneficial and detrimental effects of infusion therapy on the status of glycocalyx in sepsis; (4) considers the concept of preventing the destruction of glycocalyx as a therapeutic goal in sepsis.