CIRCULATING HEPARAN SULFATE PROFILES IN PEDIATRIC ACUTE RESPIRATORY DISTRESS SYNDROME.
Journal
Shock (Augusta, Ga.)
ISSN: 1540-0514
Titre abrégé: Shock
Pays: United States
ID NLM: 9421564
Informations de publication
Date de publication:
01 Oct 2024
01 Oct 2024
Historique:
medline:
27
9
2024
pubmed:
27
9
2024
entrez:
27
9
2024
Statut:
ppublish
Résumé
Introduction: Sepsis-induced degradation of endothelial glycocalyx heparan sulfate (HS) contributes to the pulmonary microvascular endothelial injury characteristic of acute respiratory distress syndrome (ARDS) pathogenesis. Our objectives were to (1) examine relationships between plasma indices of HS degradation and protein biomarkers of endothelial injury and (2) identify patient subgroups characterized by distinct profiles of HS degradation in children with ARDS. Methods: We analyzed prospectively collected plasma (2018-2020) from a cohort of invasively mechanically ventilated children (aged >1 month to <18 years) with ARDS. Mass spectrometry characterized and quantified patterns of HS disaccharide sulfation. Protein biomarkers reflective of endothelial injury (e.g., angiopoietin-2, vascular cell adhesion molecule-1, soluble thrombomodulin) were measured with a multiplex immunoassay. Pearson correlation coefficients were used to construct a biomarker correlation network. Centrality metrics detected influential biomarkers (i.e., network hubs). K-means clustering identified unique patient subgroups based on HS disaccharide profiles. Results: We evaluated 36 patients with pediatric ARDS. HS disaccharide sulfation patterns, 6S, NS, and NS2S, positively correlated with all biomarkers of endothelial injury (all P < 0.05) and were classified as network hubs. We identified three patient subgroups, with cluster 3 (n = 5) demonstrating elevated levels of 6S and N-sulfated HS disaccharides. In cluster 3, 60% of children were female and nonpulmonary sepsis accounted for 60% of cases. Relative to cluster 1 (n = 12), cluster 3 was associated with higher oxygen saturation index (P = 0.029) and fewer 28-day ventilator-free days (P = 0.016). Conclusions: Circulating highly sulfated HS fragments may represent emerging mechanistic biomarkers of endothelial injury and disease severity in pediatric ARDS.
Identifiants
pubmed: 39331799
doi: 10.1097/SHK.0000000000002421
pii: 00024382-202410000-00006
doi:
Substances chimiques
Heparitin Sulfate
9050-30-0
Biomarkers
0
Angiopoietin-2
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
496-504Informations de copyright
Copyright © 2024 by the Shock Society.
Déclaration de conflit d'intérêts
The authors report no conflicts of interest.
Références
Khemani RG, Smith L, López-Fernández YM, et al. Paediatric acute respiratory distress syndrome incidence and epidemiology (PARDIE): an international, observational study. Lancet Respir Med. 2019;7(2):115–128.
Ames SG, Banks RK, Zinter MS, et al. Assessment of patient health-related quality of life and functional outcomes in pediatric acute respiratory distress syndrome. Pediatr Crit Care Med. 2022;23(7):e319–e328.
Beitler JR, Thompson BT, Baron RM, et al. Advancing precision medicine for acute respiratory distress syndrome. Lancet Respir Med. 2022;10(1):107–120.
Shaver CM, Bastarache JA. Clinical and biological heterogeneity in acute respiratory distress syndrome: direct versus indirect lung injury. Clin Chest Med. 2014;35(4):639–653.
Millar FR, Summers C, Griffiths MJ, et al. The pulmonary endothelium in acute respiratory distress syndrome: insights and therapeutic opportunities. Thorax. 2016;71(5):462–473.
Jedlicka J, Becker BF, Chappell D. Endothelial glycocalyx. Crit Care Clin. 2020;36(2):217–232.
Weinbaum S, Tarbell JM, Damiano ER. The structure and function of the endothelial glycocalyx layer. Review. Annu Rev Biomed Eng. 2007;9:121–167.
Reitsma S, Slaaf DW, Vink H, et al. The endothelial glycocalyx: composition, functions, and visualization. Pflugers Arch. 2007;454(3):345–359.
LaRivière WB, Schmidt EP. The pulmonary endothelial glycocalyx in ARDS: a critical role for heparan sulfate. Current topics in membranes. 2018;82:33–52.
Schmidt EP, Yang Y, Janssen WJ, et al. The pulmonary endothelial glycocalyx regulates neutrophil adhesion and lung injury during experimental sepsis. Nat Med. 2012;18(8):1217–1223.
Inagawa R, Okada H, Takemura G, et al. Ultrastructural alteration of pulmonary capillary endothelial glycocalyx during endotoxemia. Chest. 2018;154(2):317–325.
Oshima K, Haeger SM, Hippensteel JA, et al. More than a biomarker: the systemic consequences of heparan sulfate fragments released during endothelial surface layer degradation (2017 Grover Conference Series). Pulmonary Circulation. 2018;8(1):1–10.
Liao YE, Liu J, Arnold K. Heparan sulfates and heparan sulfate binding proteins in sepsis. Front Mol Biosci. 2023;10:1146685.
Schmidt EP, Li G, Li L, et al. The circulating glycosaminoglycan signature of respiratory failure in critically ill adults. J Biol Chem. 2014;289(12):8194–8202.
Hippensteel JA, Uchimido R, Tyler PD, et al. Intravenous fluid resuscitation is associated with septic endothelial glycocalyx degradation. Crit Care. 2019;23(1):259.
Hippensteel JA, Anderson BJ, Orfila JE, et al. Circulating heparan sulfate fragments mediate septic cognitive dysfunction. J Clin Invest. 2019;129(4):1779–1784.
Sallee CJ, Hippensteel JA, Miller KR, et al. Endothelial glycocalyx degradation patterns in sepsis-associated pediatric acute respiratory distress syndrome: a single center retrospective observational study. J Intensive Care Med. 2024;39(3):277–287.
Maddux AB, Miller KR, Sierra YL, et al. Recovery trajectories in children requiring 3 or more days of invasive ventilation. Crit Care Med. 2024;52(5):798–810.
Murphy LS, Wickersham N, McNeil JB, et al. Endothelial glycocalyx degradation is more severe in patients with non-pulmonary sepsis compared to pulmonary sepsis and associates with risk of ARDS and other organ dysfunction. Ann Intensive Care. 2017;7(1):102.
Oshima K, Han X, Ouyang Y, et al. Loss of endothelial sulfatase-1 after experimental sepsis attenuates subsequent pulmonary inflammatory responses. Am J Physiol Lung Cell Mol Physiol. 2019;317(5):L667–L677.
Sun X, Li L, Overdier KH, et al. Analysis of total human urinary glycosaminoglycan disaccharides by liquid chromatography-tandem mass spectrometry. Anal Chem. 2015;87(12):6220–6227.
Yang Y, Haeger SM, Suflita MA, et al. Fibroblast growth factor signaling mediates pulmonary endothelial glycocalyx reconstitution. Am J Respir Cell Mol Biol. 2017;56(6):727–737.
Schmidt EP, Overdier KH, Sun X, et al. Urinary glycosaminoglycans predict outcomes in septic shock and acute respiratory distress syndrome. Am J Respir Crit Care Med. 2016;194(4):439–449.
Flori HR, Ware LB, Glidden D, et al. Early elevation of plasma soluble intercellular adhesion molecule-1 in pediatric acute lung injury identifies patients at increased risk of death and prolonged mechanical ventilation. Pediatr Crit Care Med. 2003;4(3):315–321.
Parsons PE, Matthay MA, Ware LB, et al; National Heart, Lung, Blood Institute Acute Respiratory Distress Syndrome Clinical Trials Network. Elevated plasma levels of soluble TNF receptors are associated with morbidity and mortality in patients with acute lung injury. Am J Physiol Lung Cell Mol Physiol. 2005;288(3):L426–L431.
Parikh SM, Mammoto T, Schultz A, et al. Excess circulating angiopoietin-2 may contribute to pulmonary vascular leak in sepsis in humans. PLoS Med. 2006;3(3):e46.
Flori HR, Ware LB, Milet M, et al. Early elevation of plasma von Willebrand factor antigen in pediatric acute lung injury is associated with an increased risk of death and prolonged mechanical ventilation. Pediatr Crit Care Med. 2007;8(2):96–101.
Calfee CS, Janz DR, Bernard GR, et al. Distinct molecular phenotypes of direct vs indirect ARDS in single-center and multicenter studies. Chest. 2015;147(6):1539–1548.
Zinter MS, Spicer A, Orwoll BO, et al. Plasma angiopoietin-2 outperforms other markers of endothelial injury in prognosticating pediatric ARDS mortality. Am J Physiol Lung Cell Mol Physiol. 2016;310(3):L224–L231.
Monteiro ACC, Flori H, Dahmer MK, et al. Thrombomodulin is associated with increased mortality and organ failure in mechanically ventilated children with acute respiratory failure: biomarker analysis from a multicenter randomized controlled trial. Crit Care. 2021;25(1):271.
Emeriaud G, Lopez-Fernandez YM, Iyer NP, et al. Executive summary of the second international guidelines for the diagnosis and management of pediatric acute respiratory distress syndrome (PALICC-2). Pediatr Crit Care Med. 2023;24(2):143–168.
Yehya N, Keim G, Thomas NJ. Subtypes of pediatric acute respiratory distress syndrome have different predictors of mortality. Intensive Care Med. 2018;44(8):1230–1239.
Pollack MM, Patel KM, Ruttimann UE. PRISM III: an updated pediatric risk of mortality score. Crit Care Med. 1996;24(5):743–752.
Leteurtre S, Duhamel A, Salleron J, et al. PELOD-2: an update of the pediatric logistic organ dysfunction score. Crit Care Med. 2013;41(7):1761–1773.
Yehya N, Harhay MO, Curley MAQ, et al. Reappraisal of ventilator-free days in critical care research. Am J Respir Crit Care Med. 2019;200(7):828–836.
Spicer AC, Calfee CS, Zinter MS, et al. A simple and robust bedside model for mortality risk in pediatric patients with acute respiratory distress syndrome. Pediatr Crit Care Med. 2016;17(10):907–916.
Zinter MS, Delucchi KL, Kong MY, et al. Early plasma matrix metalloproteinase profiles. A novel pathway in pediatric acute respiratory distress syndrome. Am J Respir Crit Care Med. 2019;199(2):181–189.
Haeger SM, Yang Y, Schmidt EP. Heparan sulfate in the developing, healthy, and injured lung. Am J Respir Cell Mol Biol. 2016;55(1):5–11.
Alfano C, Farina L, Petti M. Networks as biomarkers: uses and purposes. Gen. 2023;14(2):429.
Charitou T, Bryan K, Lynn DJ. Using biological networks to integrate, visualize and analyze genomics data. Genet Sel Evol. 2016;48:27.
Sullivan RC, Rockstrom MD, Schmidt EP, et al. Endothelial glycocalyx degradation during sepsis: causes and consequences. Matrix Biol Plus. 2021;12:100094.
Becker BF, Jacob M, Leipert S, et al. Degradation of the endothelial glycocalyx in clinical settings: searching for the sheddases. Br J Clin Pharmacol. 2015;80(3):389–402.
Rangarajan S, Richter JR, Richter RP, et al. Heparanase-enhanced shedding of syndecan-1 and its role in driving disease pathogenesis and progression. J Histochem Cytochem. 2020;68(12):823–840.
Morris A, Wang B, Waern I, et al. The role of heparanase in pulmonary cell recruitment in response to an allergic but not non-allergic stimulus. PLoS One. 2015;10(6):e0127032.
Peterson SB, Liu J. Multi-faceted substrate specificity of heparanase. Matrix Biol. 2013;32(5):223–227.
Yu Y, Williams A, Zhang X, et al. Specificity and action pattern of heparanase Bp, a beta-glucuronidase from Burkholderia pseudomallei. Glycobiology. 2019;29(8):572–581.
Sinha P, Meyer NJ, Calfee CS. Biological phenotyping in sepsis and acute respiratory distress syndrome. Annu Rev Med. 2023;74:457–471.
Calfee CS, Delucchi K, Parsons PE, et al. Subphenotypes in acute respiratory distress syndrome: latent class analysis of data from two randomised controlled trials. Lancet Respir Med. 2014;2(8):611–620.
Yehya N, Zinter MS, Thompson JM, et al. Identification of molecular subphenotypes in two cohorts of paediatric ARDS. Thorax. 2024;79(2):128–134.
Bellani G, Laffey JG, Pham T, et al. Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. JAMA. 2016;315(8):788–800.
Rogers AJ, Leligdowicz A, Contrepois K, et al. Plasma metabolites in early Sepsis identify distinct clusters defined by plasma lipids. Crit Care Explor. 2021;3(8):e0478.
Suzuki A, Tomita H, Okada H. Form follows function: the endothelial glycocalyx. Transl Res. 2022;247:158–167.
Rizzo AN, Haeger SM, Oshima K, et al. Alveolar epithelial glycocalyx degradation mediates surfactant dysfunction and contributes to acute respiratory distress syndrome. JCI Insight. 2022;7(2):e154573.
Sinha P, Spicer A, Delucchi KL, et al. Comparison of machine learning clustering algorithms for detecting heterogeneity of treatment effect in acute respiratory distress syndrome: a secondary analysis of three randomised controlled trials. EBioMedicine. 2021;74:103697.
Xu D, Esko JD. Demystifying heparan sulfate-protein interactions. Annu Rev Biochem. 2014;83:129–157.
Thacker BE, Xu D, Lawrence R, et al. Heparan sulfate 3-O-sulfation: a rare modification in search of a function. Matrix Biol. 2014;35:60–72.