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Review
. 2023 Aug 29:2023:6685251.
doi: 10.1155/2023/6685251. eCollection 2023.

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

Bingxuan Lv  1 , Shengshi Huang  2 , Hong Huang  2 , Na Niu  3 , Ju Liu  2
Affiliations
Review

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

Bingxuan Lv et al. Mediators Inflamm. .

Abstract

This review aims at summarizing state-of-the-art knowledge on glycocalyx and SARS-CoV-2. The endothelial glycocalyx is a dynamic grid overlying the surface of the endothelial cell (EC) lumen and consists of membrane-bound proteoglycans and glycoproteins. The role of glycocalyx has been determined in the regulation of EC permeability, adhesion, and coagulation. SARS-CoV-2 is an enveloped, single-stranded RNA virus belonging to β-coronavirus that causes the outbreak and the pandemic of COVID-19. Through the respiratory tract, SARS-CoV-2 enters blood circulation and interacts with ECs possessing angiotensin-converting enzyme 2 (ACE2). Intact glycolyx prevents SARS-CoV-2 invasion of ECs. When the glycocalyx is incomplete, virus spike protein of SARS-CoV-2 binds with ACE2 and enters ECs for replication. In addition, cytokine storm targets glycocalyx, leading to subsequent coagulation disorder. Therefore, it is intriguing to develop a novel treatment for SARS-CoV-2 infection through the maintenance of the integrity of glycocalyx. This review aims to summarize state-of-the-art knowledge of glycocalyx and its potential function in SARS-CoV-2 infection.

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Conflict of interest statement

The authors have no financial conflicts of interest.

Figures

Figure 1
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.
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