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Age-related differences in circulating heparanase-1 activity in sepsis and correlation with systemic vascular endotheliopathy
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DOI：10.3389/fmed.2026.1893157.png)
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Abstract
En 中文
BackgroundHeparanase-1 (HPSE)-mediated degradation of endothelial glycocalyx heparan sulfate (HS) contributes to vascular endotheliopathy in sepsis; yet age-dependent differences in HPSE biology remain undefined. Thus; we sought to determine age-related differences in circulating HPSE activity during sepsis and its association with markers of endotheliopathy and organ dysfunction.MethodsHeparanase-1 enzymatic activity and HS disaccharide levels were measured in plasma from children (10 sepsis; 10 controls) and adults (16 sepsis; 15 controls) from prospective observational cohorts using liquid chromatography-tandem mass spectrometry. Associations with plasma angiopoietin-2 levels and change in serum albumin (markers of endotheliopathy) in addition to organ failure scores were assessed using Spearman correlations.ResultsHeparanase-1 activity and circulating HS were elevated in both sepsis cohorts compared to controls; with moderate-to-strong correlations between HPSE activity and HS levels. However; adults with sepsis demonstrated approximately 10-fold higher plasma HPSE activity than children (median 1; 256 vs. 116; p < 0.001); despite children exhibiting greater endotheliopathy and higher organ failure scores. In both age groups; HPSE activity correlated with angiopoietin-2; serum albumin decline; and organ failure scores. Adult non-survivors had higher HPSE activity than survivors; no pediatric deaths occurred. Predominant neutrophilic/monocytic activation in adults versus greater platelet consumption in children may suggest developmental differences in cellular sources of circulating HPSE.ConclusionHeparanase-1-mediated glycocalyx degradation is a conserved feature of sepsis across the age spectrum; but the magnitude; cellular source; and clinical implications of circulating HPSE activity differ markedly by age; underscoring the need for age-stratified therapeutic approaches.
Keywords:
children
sepsis
adults
heparan sulfate
endothelial glycocalyx
heparanase activity
vascular endotheliopathy
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