Endothelial Glycocalyx Injury in SARS-CoV-2 Infection: Molecular Mechanisms and Potential Targeted Therapy

Figure 1

Schematic representation of the process of SARS-CoV-2 invasion through endothelial glycocalyx. The invasion of SARS-CoV-2 to endothelial cells disrupts glycocalyx. SARS-CoV-2 exploits HS to facilitate the attachment of spike-bearing viral particles to the cell surface through the glycocalyx. S1 of SARS-CoV-2 binds with ACE2, which suppresses the amount of HA synthase and promotes the production of ROS. ROS activates glycocalyx sheddases, including hyaluronidases, MMPs, and heparinases. Hyaluronidases cleave HA. MMPs cleave syndecan ectodomain, CS, and HS. Heparinases cleave HS. In addition, SARS-CoV-2 infection increases the level of Angpt-2, which activates heparanase release, consequently leading to degradation of the endothelial glycocalyx. HA, hyaluronic acid; HS, heparan sulfate (HS); CS, chondroitin sulfate. ROS, reactive oxygen species; MMP, matrix metalloproteases.