{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T18:08:50Z","timestamp":1778782130565,"version":"3.51.4"},"posted":{"date-parts":[[2026,5,12]]},"group-title":"Cell Biology","reference-count":33,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R35GM146859"],"award-info":[{"award-number":["R35GM146859"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R35GM137958"],"award-info":[{"award-number":["R35GM137958"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01HL171594"],"award-info":[{"award-number":["R01HL171594"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01HL182062"],"award-info":[{"award-number":["R01HL182062"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Mechanisms that promote organ injury after trauma and hemorrhagic shock (T\/HS) remain poorly defined. Endothelial heparan sulfates with a 3-O-sulfate (3-OS) modification, controlled by the HS3ST1 gene, have anticoagulant and anti-inflammatory properties through their interaction with antithrombin. Our objective was to determine whether HS3ST1 deficiency drives organ injury and poor outcomes after T\/HS.\n                  <jats:italic>Hs3st1<\/jats:italic>\n                  <jats:sup>-\/-<\/jats:sup>\n                  and wild-type (WT) mice were subjected to T\/HS followed by resuscitation with lactated ringer\u2019s (LR) or fresh frozen plasma (FFP). While no differences were observed between WT and\n                  <jats:italic>Hs3st1<\/jats:italic>\n                  <jats:sup>-\/-<\/jats:sup>\n                  LR resuscitated mice, lung injury and leukocyte infiltrates were significantly increased in FFP resuscitated\n                  <jats:italic>Hs3st1<\/jats:italic>\n                  <jats:sup>-\/-<\/jats:sup>\n                  compared to WT mice. In vitro, leukocyte slow rolling and adherence was increased in HS3ST1 KO compared to WT cells. Among 472 T\/HS patients, of which 31 (7%) were homozygous for the rs16881446 variant allele (GG), the number of ventilator free days was lower, and mortality was significantly higher in AG and GG patients. The rs16881446 genotype was independently associated with mortality. In conclusion, HS3ST1 deficiency mitigates organ protection from FFP resuscitation, partly through mediating EC:leukocyte engagement, and predicts mortality after T\/HS. These findings identify a novel therapeutic target and prognostic tool that can be leveraged towards improved risk stratification after trauma.\n                <\/jats:p>","DOI":"10.64898\/2026.05.07.723543","type":"posted-content","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T15:55:25Z","timestamp":1778601325000},"source":"Crossref","is-referenced-by-count":0,"title":["HS3ST1 regulates pulmonary inflammation and is a determinant of clinical outcomes after trauma and hemorrhagic shock"],"prefix":"10.64898","author":[{"given":"Ava K.","family":"Mokhtari","sequence":"first","affiliation":[{"name":"The University of Colorado-Denver\/Anschutz Medical Campus, Department of Surgery, Division of Gastrointestinal, Trauma, and Endocrine Surgery, Aurora, CO"},{"name":"Baylor College of Medicine, Department of Surgery, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madeline E.","family":"Cotton","sequence":"additional","affiliation":[{"name":"The University of Texas Health Science Center and the McGovern School of Medicine, Department of Surgery, Division of Acute Care Surgery, and the Center for Translational Injury Research, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimberly A.","family":"Thomas","sequence":"additional","affiliation":[{"name":"The University of Colorado-Denver\/Anschutz Medical Campus, Department of Pathology, Aurora, CO"},{"name":"Vitalant Research Institute, Denver, CO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alisha","family":"Chitrakar","sequence":"additional","affiliation":[{"name":"Vitalant Research Institute, Denver, CO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph D.","family":"Krocker","sequence":"additional","affiliation":[{"name":"The University of Texas Health Science Center and the McGovern School of Medicine, Department of Surgery, Division of Acute Care Surgery, and the Center for Translational Injury Research, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marissa","family":"Pokharel","sequence":"additional","affiliation":[{"name":"The University of Colorado-Denver\/Anschutz Medical Campus, Department of Surgery, Division of Gastrointestinal, Trauma, and Endocrine Surgery, Aurora, CO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baron K.","family":"Osborn","sequence":"additional","affiliation":[{"name":"The University of Colorado-Denver\/Anschutz Medical Campus, Department of Surgery, Division of Gastrointestinal, Trauma, and Endocrine Surgery, Aurora, CO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"del Pilar Huby Vidaurre","sequence":"additional","affiliation":[{"name":"The University of Texas Health Science Center and the McGovern School of Medicine, Department of Surgery, Division of Acute Care Surgery, and the Center for Translational Injury Research, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atharwa R.","family":"Mankame","sequence":"additional","affiliation":[{"name":"The University of Colorado-Denver\/Anschutz Medical Campus, Department of Surgery, Division of Gastrointestinal, Trauma, and Endocrine Surgery, Aurora, CO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles E.","family":"Wade","sequence":"additional","affiliation":[{"name":"The University of Texas Health Science Center and the McGovern School of Medicine, Department of Surgery, Division of Acute Care Surgery, and the Center for Translational Injury Research, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yao-Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"The University of Texas Health Science Center and the McGovern School of Medicine, Department of Surgery, Division of Acute Care Surgery, and the Center for Translational Injury Research, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David J.","family":"Orlicky","sequence":"additional","affiliation":[{"name":"The University of Colorado-Denver\/Anschutz Medical Campus, Department of Pathology, Aurora, CO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitchell J.","family":"Cohen","sequence":"additional","affiliation":[{"name":"The University of Colorado-Denver\/Anschutz Medical Campus, Department of Surgery, Division of Gastrointestinal, Trauma, and Endocrine Surgery, Aurora, CO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jillian R.","family":"Richter","sequence":"additional","affiliation":[{"name":"The University of Alabama, Birmingham, Department of Surgery and Center for Injury Science, Division of Trauma and Acute Care Surgery, Birmingham, AL"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas W.","family":"Shworak","sequence":"additional","affiliation":[{"name":"The George Washington University, Department of Pharmacology, Washington, DC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica C.","family":"Cardenas","sequence":"additional","affiliation":[{"name":"The University of Colorado-Denver\/Anschutz Medical Campus, Department of Surgery, Division of Gastrointestinal, Trauma, and Endocrine Surgery, Aurora, CO"},{"name":"The University of Texas Health Science Center and the McGovern School of Medicine, Department of Surgery, Division of Acute Care Surgery, and the Center for Translational Injury Research, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"issue":"1","key":"2026051410153145000_2026.05.07.723543v1.1","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.injury.2016.10.037","article-title":"Trends in 1029 trauma deaths at a level 1 trauma center: Impact of a bleeding control bundle of 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