Therapeutic strategies targeting the endothelial glycocalyx

Abstract

Purpose of review: This review will highlight recent studies that have examined the endothelial glycocalyx in a variety of health conditions, as well as potential glycocalyx-targeted therapies.

Recent findings: A degraded glycocalyx is present in individuals that consume high sodium diet or have kidney disease, diabetes, preeclampsia, coronavirus disease 2019 (COVID-19), or sepsis. Specifically, these conditions are accompanied by elevated glycocalyx components in the blood, such as syndecan-1, syndecans-4, heparin sulfate, and enhanced heparinase activity. Impaired glycocalyx barrier function is accompanied by decreased nitric oxide bioavailability, increased leukocyte adhesion to endothelial cells, and vascular permeability. Glycocalyx degradation appears to play a key role in the progression of cardiovascular complications. However, studies that have used glycocalyx-targeted therapies to treat these conditions are scarce. Various therapeutics can restore the glycocalyx in kidney disease, diabetes, COVID-19, and sepsis. Exposing endothelial cells to glycocalyx components, such as heparin sulfate and hyaluronan protects the glycocalyx.

Summary: We conclude that the glycocalyx is degraded in a variety of health conditions, although it remains to be determined whether glycocalyx degradation plays a causal role in disease progression and severity, and whether glycocalyx-targeted therapies improve patient health outcomes. Future studies are warranted to investigate therapeutic strategies that target the endothelial glycocalyx.

Figure 1:

Image of the endothelial glycocalyx in a mouse soleus capillary captured via electron microscopy (scale bar = 500 μm).

Figure 2:

In its normal state, the endothelial glycocaly protects the endothelium from the contents of blood. The glycocalyx mechanotransduces shear stress to the endothelium, which promotes nitric oxide-mediated vasodilation. In its degraded state, components of the endothelial glycocalyx can be found in the blood, and the vasoprotective functions of the glycocalyx are inhibited.