CIRCULATING HEPARAN SULFATE PROFILES IN PEDIATRIC ACUTE RESPIRATORY DISTRESS SYNDROME.

Autor:	Sallee CJ; Department of Pediatrics, Division of Pediatric Critical Care Medicine, David Geffen School of Medicine at University of California Los Angeles and Mattel Children's Hospital, Los Angeles, California., Maddux AB; Department of Pediatrics, Section of Pediatric Critical Care, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, Colorado., Hippensteel JA; Department of Medicine, Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado., Markovic D; Department of Medicine, Biostatistics Core, University of California Los Angeles, Los Angeles, California., Oshima K; Department of Medicine, Division of Pulmonary and Critical Care Medicine, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts., Schwingshackl A; Department of Pediatrics, Division of Pediatric Critical Care Medicine, David Geffen School of Medicine at University of California Los Angeles and Mattel Children's Hospital, Los Angeles, California., Mourani PM; Department of Pediatrics, Division of Pediatric Critical Care Medicine, University of Arkansas for Medical Sciences and Arkansas Children's Hospital, Little Rock, Arkansas., Schmidt EP; Department of Medicine, Division of Pulmonary and Critical Care Medicine, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts., Sapru A; Department of Pediatrics, Division of Pediatric Critical Care Medicine, David Geffen School of Medicine at University of California Los Angeles and Mattel Children's Hospital, Los Angeles, California.
Jazyk:	angličtina
Zdroj:	Shock (Augusta, Ga.) [Shock] 2024 Oct 01; Vol. 62 (4), pp. 496-504.
DOI:	10.1097/SHK.0000000000002421
Abstrakt:	Abstract: 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. Competing Interests: The authors report no conflicts of interest. (Copyright © 2024 by the Shock Society.)
Databáze:	MEDLINE
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