# Vascular endothelial injury exacerbates coronavirus disease 2019: The role of endothelial glycocalyx protection

**Authors:** Hideshi Okada, Shozo Yoshida, Akira Hara, Shinji Ogura, Hiroyuki Tomita

PMC · DOI: 10.1111/micc.12654 · 2020-08-30

## TL;DR

This review explores how vascular endothelial injury, particularly involving the glycocalyx, may worsen the severity of COVID-19 and suggests it as a potential therapeutic target.

## Contribution

The paper highlights the glycocalyx as a novel therapeutic target for systemic complications in COVID-19.

## Key findings

- Vascular endothelial injury and glycocalyx damage may contribute to systemic complications in COVID-19.
- The glycocalyx plays a key role in capillary homeostasis and is particularly vulnerable in the lungs.
- Targeting the glycocalyx could offer new treatment strategies for severe COVID-19.

## Abstract

The potential for a rapid increase in severity is among the most frightening aspects of severe acute respiratory syndrome coronavirus 2 infection. Evidence increasingly suggests that the symptoms of coronavirus disease‐2019 (COVID‐19)‐related acute respiratory distress syndrome (ARDS) differ from those of classic ARDS. Recently, the severity of COVID‐19 has been attributed to a systemic, thrombotic, and inflammatory disease that damages not only the lungs but also multiple organs, including the heart, brain, toes, and liver. This systemic form of COVID‐19 may be due to inflammation and vascular endothelial cell injury. The vascular endothelial glycocalyx comprises glycoproteins and plays an important role in systemic capillary homeostasis maintenance. The glycocalyx covers the entire vascular endothelium, and its thickness varies among organs. The endothelial glycocalyx is very thin in the pulmonary capillaries, where it is affected by gaseous exchange with the alveoli and the low intravascular pressure in the pulmonary circulation. Despite the clearly important roles of the glycocalyx in vascular endothelial injury, thrombosis, vasculitis, and inflammation, the link between this structure and vascular endothelial cell dysfunction in COVID‐19 remains unclear. In this prospective review, we summarize the importance of the glycocalyx and its potential as a therapeutic target in cases of systemic COVID‐19.

## Linked entities

- **Diseases:** coronavirus disease-2019 (MONDO:0100096), acute respiratory distress syndrome (MONDO:0006502), vasculitis (MONDO:0018882)

## Full-text entities

- **Genes:** F3 (coagulation factor III, tissue factor) [NCBI Gene 2152] {aka CD142, TF, TFA}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, TFPI (tissue factor pathway inhibitor) [NCBI Gene 7035] {aka EPI, LACI, TFI, TFPI1}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, SDC1 (syndecan 1) [NCBI Gene 6382] {aka CD138, SDC, SYND1, syndecan}, THBD (thrombomodulin) [NCBI Gene 7056] {aka AHUS6, BDCA-3, BDCA3, CD141, THPH12, THRM}, ELANE (elastase, neutrophil expressed) [NCBI Gene 1991] {aka ELA2, GE, HLE, HNE, NE, PMN-E}, F2 (coagulation factor II, thrombin) [NCBI Gene 2147] {aka PT, RPRGL2, THPH1}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, ACE2 (angiotensin converting enzyme 2) [NCBI Gene 59272] {aka ACEH}, PROC (protein C, inactivator of coagulation factors Va and VIIIa) [NCBI Gene 5624] {aka APC, PC, PROC1, THPH3, THPH4}
- **Diseases:** ARDS (MESH:D012128), hypertriglyceridemia (MESH:D015228), diabetes (MESH:D003920), respiratory disease (MESH:D012140), blood complications (MESH:D006402), fibrosis (MESH:D005355), radiographic opacities (MESH:D003318), albuminuria (MESH:D000419), COVID-19 ARDS (MESH:D000086382), GATEKEEPER OF VASCULAR (MESH:D057772), cerebral infarction (MESH:D002544), alveolar damage (MESH:D055370), viral infection (MESH:D014777), sepsis (MESH:D018805), edema (MESH:D004487), Kawasaki disease (MESH:D009080), infectious diseases (MESH:D003141), Microvascular disorders (MESH:D017566), influenza (MESH:D007251), heart failure (MESH:D006333), blood clots (MESH:D013927), organ failure (MESH:D009102), L disease (MESH:D005645), Inflammation (MESH:D007249), acute kidney injury (MESH:D058186), died (MESH:D003643), ENDOTHELIAL (MESH:D005642), HT (MESH:D006973), cardiovascular disease (MESH:D002318), walls (MESH:D056988), -coagulation (MESH:D001778), trauma (MESH:D014947), critically ill (MESH:D016638), Middle East respiratory syndrome (MESH:D018352), dysfunction (MESH:D006331), stroke (MESH:D020521), hyperglycemia (MESH:D006943), II pneumocyte hyperplasia (MESH:C538236), cardiovascular abnormalities (MESH:D018376), ischemia (MESH:D007511), venous thromboembolism (MESH:D054556), Bleeding dysfunctions (MESH:D006470), hypoxemia (MESH:D000860), vasculitis (MESH:D014657), infection (MESH:D007239), non-cardiogenic pulmonary edema (MESH:D011654), OTHER DISEASES (MESH:D004194), endothelial cell dysfunction (MESH:D055954), chronic kidney disease (MESH:D051436), endothelial dysfunction (MESH:D014652), lung damage (MESH:D008171), SARS (MESH:D045169)
- **Chemicals:** GAG (MESH:D006025), LPS (MESH:D008070), lanthanum nitrate (MESH:C016534), Hyaluronic acid (MESH:D006820), sivelestat (MESH:C069195), sugar (MESH:D000073893), oxygen (MESH:D010100), heparin sulfate (-)
- **Species:** Homo sapiens (human, species) [taxon 9606], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Mus musculus (house mouse, species) [taxon 10090]

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC7435519/full.md

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Source: https://tomesphere.com/paper/PMC7435519