Vascular Endothelial Glycocalyx Damage and Potential Targeted Therapy in COVID-19

Zha, Duoduo; Fu, Mingui; Qian, Yisong

doi:10.3390/cells11121972

Cited by 21 publications

(13 citation statements)

References 147 publications

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Section: Markers Of Endothelial Dysfunction In Covid-19mentioning

confidence: 99%

“…The glycocalyx, a protective microstructure layer on the vascular endothelium, consists of glycoproteins and regulates capillary homeostasis by controlling vascular inflammation [ 109 ]. Glycocalyx layer regulates vascular barrier integrity, leukocyte adhesion, mechanosensing, mechanotransduction, anti-inflammatory and anti-thrombotic functions [ 109 ]. Emerging evidence has suggested that thinning of endothelial glycocalyx layer is associated with COVID-19, and thus the glycocalyx integrity was perceived as an important therapeutic target in COVID-19 [ 109 , 110 ].…”

Section: Markers Of Endothelial Dysfunction In Covid-19mentioning

confidence: 99%

“…Glycocalyx layer regulates vascular barrier integrity, leukocyte adhesion, mechanosensing, mechanotransduction, anti-inflammatory and anti-thrombotic functions [ 109 ]. Emerging evidence has suggested that thinning of endothelial glycocalyx layer is associated with COVID-19, and thus the glycocalyx integrity was perceived as an important therapeutic target in COVID-19 [ 109 , 110 ]. Glycocalyx degradation and shedding disrupts endothelial junctional stability and plays a pivotal role in various forms of cardiovascular diseases [ 111 ].…”

Section: Markers Of Endothelial Dysfunction In Covid-19mentioning

confidence: 99%

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Endothelial dysfunction in COVID-19: an overview of evidence, biomarkers, mechanisms and potential therapies

2022

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The fight against coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection is still raging. However, the pathophysiology of acute and post-acute manifestations of COVID-19 (long COVID-19) is understudied. Endothelial cells are sentinels lining the innermost layer of blood vessel that gatekeep micro- and macro-vascular health by sensing pathogen/danger signals and secreting vasoactive molecules. SARS-CoV-2 infection primarily affects the pulmonary system, but accumulating evidence suggests that it also affects the pan-vasculature in the extrapulmonary systems by directly (via virus infection) or indirectly (via cytokine storm), causing endothelial dysfunction (endotheliitis, endothelialitis and endotheliopathy) and multi-organ injury. Mounting evidence suggests that SARS-CoV-2 infection leads to multiple instances of endothelial dysfunction, including reduced nitric oxide (NO) bioavailability, oxidative stress, endothelial injury, glycocalyx/barrier disruption, hyperpermeability, inflammation/leukocyte adhesion, senescence, endothelial-to-mesenchymal transition (EndoMT), hypercoagulability, thrombosis and many others. Thus, COVID-19 is deemed as a (micro)vascular and endothelial disease. Of translational relevance, several candidate drugs which are endothelial protective have been shown to improve clinical manifestations of COVID-19 patients. The purpose of this review is to provide a latest summary of biomarkers associated with endothelial cell activation in COVID-19 and offer mechanistic insights into the molecular basis of endothelial activation/dysfunction in macro- and micro-vasculature of COVID-19 patients. We envisage further development of cellular models and suitable animal models mimicking endothelial dysfunction aspect of COVID-19 being able to accelerate the discovery of new drugs targeting endothelial dysfunction in pan-vasculature from COVID-19 patients.

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Section: Markers Of Endothelial Dysfunction In Covid-19mentioning

confidence: 99%

Section: Markers Of Endothelial Dysfunction In Covid-19mentioning

confidence: 99%

Section: Markers Of Endothelial Dysfunction In Covid-19mentioning

confidence: 99%

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Endothelial dysfunction in COVID-19: an overview of evidence, biomarkers, mechanisms and potential therapies

2022

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“…Mechanistically, the inflammatory mediators, reactive oxygen species, matrix metalloproteases, the glycocalyx, fragments, and the viral proteins may contribute to endothelial glycocalyx damage in COVID-19 ( Zha et al, 2022 ). Heparin sulfate (HS) has been shown to regulate the activation of the bradykinin pathway, which is involved in local inflammation and vascular permeability ( Buijsers et al, 2020 ).…”

Section: Ed Related To Covid-19—lesson For Pascmentioning

confidence: 99%

Pathogenic mechanisms of post-acute sequelae of SARS-CoV-2 infection (PASC)

Sherif

Gómez

Connors

et al. 2023

eLife

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COVID-19, with persistent and new onset of symptoms such as fatigue, post-exertional malaise, and cognitive dysfunction that last for months and impact everyday functioning, is referred to as Long COVID under the general category of post-acute sequelae of SARS-CoV-2 infection (PASC). PASC is highly heterogenous and may be associated with multisystem tissue damage/dysfunction including acute encephalitis, cardiopulmonary syndromes, fibrosis, hepatobiliary damages, gastrointestinal dysregulation, myocardial infarction, neuromuscular syndromes, neuropsychiatric disorders, pulmonary damage, renal failure, stroke, and vascular endothelial dysregulation. A better understanding of the pathophysiologic mechanisms underlying PASC is essential to guide prevention and treatment. This review addresses potential mechanisms and hypotheses that connect SARS-CoV-2 infection to long-term health consequences. Comparisons between PASC and other virus-initiated chronic syndromes such as myalgic encephalomyelitis/chronic fatigue syndrome and postural orthostatic tachycardia syndrome will be addressed. Aligning symptoms with other chronic syndromes and identifying potentially regulated common underlining pathways may be necessary for understanding the true nature of PASC. The discussed contributors to PASC symptoms include sequelae from acute SARS-CoV-2 injury to one or more organs, persistent reservoirs of the replicating virus or its remnants in several tissues, re-activation of latent pathogens such as Epstein–Barr and herpes viruses in COVID-19 immune-dysregulated tissue environment, SARS-CoV-2 interactions with host microbiome/virome communities, clotting/coagulation dysregulation, dysfunctional brainstem/vagus nerve signaling, dysautonomia or autonomic dysfunction, ongoing activity of primed immune cells, and autoimmunity due to molecular mimicry between pathogen and host proteins. The individualized nature of PASC symptoms suggests that different therapeutic approaches may be required to best manage specific patients.

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“…Indeed, patients ≥70 had higher plasma levels of biomarkers reflective of endothelial cell activation (sThrombomodulin, sVCAM-1), a more disturbed glycocalyx function (syndecan), and a more disrupted barrier function (angiopoietin-2). Loss of glycocalyx is an important feature of endothelial dysfunction in COVID-19 [ 29 , 30 ]. The glycocalyx consists of proteoglycans and glycosaminoglycans that inhibit immune activation and provide an anticoagulant surface [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Age-related changes in plasma biomarkers and their association with mortality in COVID-19

et al. 2023

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BackgroundCOVID-19-induced mortality occurs predominantly in older patients. Several immunomodulating therapies seem less beneficial in these patients. The biological substrate behind these observations is unknown. The aim of this study was to obtain insight into the association between ageing, the host response, and mortality in patients with COVID-19.MethodsWe determined 43 biomarkers reflective of alterations in four pathophysiological domains: endothelial cell and coagulation activation, inflammation and organ damage, and cytokine and chemokine release. We used mediation analysis to associate ageing-driven alterations in the host response with 30-day mortality. Biomarkers associated with both ageing and mortality were validated in an intensive care unit and external cohort.Results464 general ward patients with COVID-19 were stratified according to age decades. Increasing age was an independent risk factor for 30-day mortality. Ageing was associated with alterations in each of the host response domains, characterised by greater activation of the endothelium and coagulation system and stronger elevation of inflammation and organ damage markers, which was independent of an increase in age-related comorbidities. Soluble tumor necrosis factor receptor 1, soluble triggering receptor expressed on myeloid cells 1, and soluble thrombomodulin showed the strongest correlation with ageing and explained part of the ageing-driven increase in 30-day mortality (proportion mediated: 13.0%, 12.9% and 12.6%, respectively).ConclusionAgeing is associated with a strong and broad modification of the host response to COVID-19, and specific immune changes likely contribute to increased mortality in older patients. These results may provide insight into potential age-specific immunomodulatory targets in COVID-19.

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Vascular Endothelial Glycocalyx Damage and Potential Targeted Therapy in COVID-19

Cited by 21 publications

References 147 publications

Endothelial dysfunction in COVID-19: an overview of evidence, biomarkers, mechanisms and potential therapies

Endothelial dysfunction in COVID-19: an overview of evidence, biomarkers, mechanisms and potential therapies

Pathogenic mechanisms of post-acute sequelae of SARS-CoV-2 infection (PASC)

Age-related changes in plasma biomarkers and their association with mortality in COVID-19

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