Biological Effects of Intravenous Vitamin C on Neutrophil Extracellular Traps and the Endothelial Glycocalyx in Patients with Sepsis-Induced ARDS

Qiao, Xinhua; Kashiouris, Markos; L’Heureux, Michael; Fisher, Bernard; Leichtle, Stefan W.; Truwit, Jonathon D.; Nanchal, Rahul; Hite, R. Duncan; Morris, Peter E.; Martin, Greg S.; Sevransky, Jonathan; Fowler, Alpha A.

doi:10.3390/nu14204415

Cited by 20 publications

(16 citation statements)

References 40 publications

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“…Aspirin inhibits neutrophil migration and thromboxane-dependent NETs formation by inhibiting platelet-neutrophil interactions ( 301 ). High-dose intravenous vitamin C (HDIVC) improves ARDS by reducing the occurrence of NETosis and the shedding of the vascular endothelial glycocalyx by down-regulating the expression of cell-free DNA in neutrophils and proteoglycan syndecan-1 in vascular endothelial cells ( 302 ). α1-antitrypsin (AAT), as a protease inhibitor, especially a NE inhibitor, inhibits neutrophil migration and NETs formation by binding to IL-8 to inhibit CXCR1/CXCL8 signaling axis ( 303 ).…”

Section: Potential Therapeutic Targets For Septic Ardsmentioning

confidence: 99%

The role of G protein-coupled receptor in neutrophil dysfunction during sepsis-induced acute respiratory distress syndrome

Wang

Zhu²,

Liu³

et al. 2023

Front. Immunol.

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Sepsis is defined as a life-threatening dysfunction due to a dysregulated host response to infection. It is a common and complex syndrome and is the leading cause of death in intensive care units. The lungs are most vulnerable to the challenge of sepsis, and the incidence of respiratory dysfunction has been reported to be up to 70%, in which neutrophils play a major role. Neutrophils are the first line of defense against infection, and they are regarded as the most responsive cells in sepsis. Normally, neutrophils recognize chemokines including the bacterial product N-formyl-methionyl-leucyl-phenylalanine (fMLP), complement 5a (C5a), and lipid molecules Leukotriene B4 (LTB4) and C-X-C motif chemokine ligand 8 (CXCL8), and enter the site of infection through mobilization, rolling, adhesion, migration, and chemotaxis. However, numerous studies have confirmed that despite the high levels of chemokines in septic patients and mice at the site of infection, the neutrophils cannot migrate to the proper target location, but instead they accumulate in the lungs, releasing histones, DNA, and proteases that mediate tissue damage and induce acute respiratory distress syndrome (ARDS). This is closely related to impaired neutrophil migration in sepsis, but the mechanism involved is still unclear. Many studies have shown that chemokine receptor dysregulation is an important cause of impaired neutrophil migration, and the vast majority of these chemokine receptors belong to the G protein-coupled receptors (GPCRs). In this review, we summarize the signaling pathways by which neutrophil GPCR regulates chemotaxis and the mechanisms by which abnormal GPCR function in sepsis leads to impaired neutrophil chemotaxis, which can further cause ARDS. Several potential targets for intervention are proposed to improve neutrophil chemotaxis, and we hope that this review may provide insights for clinical practitioners.

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Section: Potential Therapeutic Targets For Septic Ardsmentioning

confidence: 99%

The role of G protein-coupled receptor in neutrophil dysfunction during sepsis-induced acute respiratory distress syndrome

Wang

Zhu²,

Liu³

et al. 2023

Front. Immunol.

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“…These candidates primarily target the expression of EG degradation products, like syndecan-1, or enzymes like HPA. Clinical studies have shown that high-dose intravenous vitamin C can significantly reduce ARDS-associated syndecan-1 levels, further validating EG as an effective therapeutic target ( Qiao et al, 2022 ). Secondly, EG-related biomarkers are being examined in clinical studies to determine their reliability as indicators for ARDS diagnosis or prognosis.…”

Section: Discussionmentioning

confidence: 99%

Global research progress of endothelial cells and ALI/ARDS: a bibliometric analysis

Zhou,

Long,

Chen

et al. 2024

Front. Physiol.

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BackgroundAcute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are severe respiratory conditions with complex pathogenesis, in which endothelial cells (ECs) play a key role. Despite numerous studies on ALI/ARDS and ECs, a bibliometric analysis focusing on the field is lacking. This study aims to fill this gap by employing bibliometric techniques, offering an overarching perspective on the current research landscape, major contributors, and emerging trends within the field of ALI/ARDS and ECs.MethodsLeveraging the Web of Science Core Collection (WoSCC) database, we conducted a comprehensive search for literature relevant to ALI/ARDS and ECs. Utilizing Python, VOSviewer, and CiteSpace, we performed a bibliometric analysis on the corpus of publications within this field.ResultsThis study analyzed 972 articles from 978 research institutions across 40 countries or regions, with a total of 5,277 authors contributing. These papers have been published in 323 different journals, spanning 62 distinct research areas. The first articles in this field were published in 2011, and there has been a general upward trend in annual publications since. The United States, Germany, and China are the principal contributors, with Joe G. N. Garcia from the University of Arizona identified as the leading authority in this field. American Journal of Physiology-Lung Cellular and Molecular Physiology has the highest publication count, while Frontiers in Immunology has been increasingly focusing on this field in recent years. “Cell Biology” stands as the most prolific research area within the field. Finally, this study identifies endothelial glycocalyx, oxidative stress, pyroptosis, TLRs, NF-κB, and NLRP3 as key terms representing research hotspots and emerging frontiers in this field.ConclusionThis bibliometric analysis provides a comprehensive overview of the research landscape surrounding ALI/ARDS and ECs. It reveals an increasing academic focus on ALI/ARDS and ECs, particularly in the United States, Germany, and China. Our analysis also identifies several emerging trends and research hotspots, such as endothelial glycocalyx, oxidative stress, and pyroptosis, indicating directions for future research. The findings can guide scholars, clinicians, and policymakers in targeting research gaps and setting priorities to advance the field.

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“…Vitamin C and recombinant thrombomodulin have also been investigated to preserve the glycocalyx and improve outcomes in sepsis. In humans, 48 h of high-dose intravenous vitamin C (50 mg/kg every 6 h) lowered plasma syndecan-1 concentrations [60]. Treatment recombinant thrombomodulin normalized glycocalyx characteristics in septic mice demonstrated by lower plasma syndecan-1 concentrations after treatment [59].…”

Section: Sepsismentioning

confidence: 97%

Therapeutic strategies targeting the endothelial glycocalyx

Machin

Sabouri

Zheng

et al. 2023

Current Opinion in Clinical Nutrition &Amp; Metabolic Care

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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.

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Biological Effects of Intravenous Vitamin C on Neutrophil Extracellular Traps and the Endothelial Glycocalyx in Patients with Sepsis-Induced ARDS

Cited by 20 publications

References 40 publications

The role of G protein-coupled receptor in neutrophil dysfunction during sepsis-induced acute respiratory distress syndrome

The role of G protein-coupled receptor in neutrophil dysfunction during sepsis-induced acute respiratory distress syndrome

Global research progress of endothelial cells and ALI/ARDS: a bibliometric analysis

Therapeutic strategies targeting the endothelial glycocalyx

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