{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T06:31:10Z","timestamp":1786516270665,"version":"build-2736575974"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Heparanase-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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Heparanase-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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Heparanase-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,\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Heparanase-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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1893157","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T05:57:01Z","timestamp":1786514221000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Age-related differences in circulating heparanase-1 activity in sepsis and correlation with systemic vascular endotheliopathy"],"prefix":"10.3389","volume":"13","author":[{"given":"Colin J.","family":"Sallee","sequence":"first","affiliation":[{"name":"Division of Pediatric Critical Care Medicine, Department of Pediatrics, David Geffen School of Medicine, University of California","place":["Los Angeles, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron S.","family":"Noa","sequence":"additional","affiliation":[{"name":"Heersink School of Medicine, University of Alabama at Birmingham","place":["Birmingham, AL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mouli","family":"Bhowmik","sequence":"additional","affiliation":[{"name":"Division of Pediatric Critical Care Medicine, Department of Pediatrics, Heersink School of Medicine, University of Alabama at Birmingham","place":["Birmingham, AL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amber C.","family":"Nobles","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Heersink School of Medicine, University of Alabama at Birmingham","place":["Birmingham, AL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhangjie","family":"Wang","sequence":"additional","affiliation":[{"name":"Glycan Therapeutics","place":["Raleigh, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill","place":["Chapel Hill, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jillian R.","family":"Richter","sequence":"additional","affiliation":[{"name":"Division of Trauma and Acute Care Surgery, Department of Surgery, Heersink School of Medicine, University of Alabama at Birmingham","place":["Birmingham, AL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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