{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:42:26Z","timestamp":1790084546591,"version":"4.0.1"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM142304"],"award-info":[{"award-number":["GM142304"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL171101"],"award-info":[{"award-number":["R01HL171101"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K08GM144788"],"award-info":[{"award-number":["K08GM144788"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Haul Pediatric Research Institute"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Heparanase-1 (HPSE) is the only mammalian endo-\u03b2-D-glucuronidase that cleaves heparan sulfate (HS) polysaccharides on cell surfaces and in extracellular matrices. HPSE contributes to diverse pathological conditions, particularly in the processes driving injury to the luminal glycocalyx overlying vascular endothelial cells. Existing methods for assaying the activity of HPSE are insensitive and lack specificity. Here, we present a new method, Single Heparan Sulfate Substrate-Based Isotope Dilution Mass Spectrometry (SHS-IDMS), that permits the quantitative measurement of HPSE activity in complex biological matrices like plasma. The method involves the use of a structurally defined-HS 12-mer substrate that yields a consistent disaccharide product upon HPSE digestion. The disaccharide product is quantified using LC\u2013MS\/MS and a 13C-labeled disaccharide calibrant. The method demonstrates strong linearity, high sensitivity, and resistance to interference by heparanase-2 (HPSE-2). Using this method, we detected significant, quantitative differences in HPSE activity using 20\u00a0\u03bcL plasma samples from children with sepsis compared to samples from healthy children. Moreover, we found that plasma HPSE activity correlated with circulating levels of syndecan-1 and angiopoietin-2, supporting the hypothesis that HPSE may contribute to endothelial glycocalyx injury and pathological endothelial activation under septic conditions. The new method will advance research in the biology of this important enzyme.<\/jats:p>","DOI":"10.1093\/glycob\/cwag028","type":"journal-article","created":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T11:37:59Z","timestamp":1775907479000},"source":"Crossref","is-referenced-by-count":3,"title":["Development of a sensitive and specific method to measure heparanase activity in complex biological matrices"],"prefix":"10.1093","volume":"36","author":[{"given":"Zhangjie","family":"Wang","sequence":"first","affiliation":[{"name":"Glycan Therapeutics , 617 Hutton Street, Raleigh, NC 27606,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Richter","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Alabama at Birmingham Heersink School of Medicine , Birmingham, AL 35233-1771,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guowei","family":"Su","sequence":"additional","affiliation":[{"name":"Glycan Therapeutics , 617 Hutton Street, Raleigh, NC 27606,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongmei","family":"Xu","sequence":"additional","affiliation":[{"name":"Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina , Chapel Hill, NC 27599,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yannic","family":"Becker","sequence":"additional","affiliation":[{"name":"Mount Desert Island Biological Laboratory , Bar Harbor, ME 04609,","place":["United States"]},{"name":"Department of Nephrology, Hanover Medical School , Carl-Neiber-Stra\u03b2e 1,30625 Hanover 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