{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:59:18Z","timestamp":1790189958439,"version":"4.1.0"},"reference-count":52,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Traumatic brain injury (TBI) results in the release of microparticles from injured brain cells into circulation. These microparticles induce a systemic hypercoagulable state that rapidly transitions into secondary coagulopathy and endotheliopathy. We hypothesize that removing these microparticles from circulation could mitigate the TBI-induced secondary pathologies and improve outcomes. In this study, we investigated the role of Gas-6 (growth arrest\u2013specific 6) as a scavenging factor for microparticles.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>We quantified plasma Gas-6 levels in a mouse model of TBI and administered exogenous Gas-6 either before or after TBI to evaluate its effects on endotheliopathy, coagulopathy, and outcomes. Mechanistic studies assessed Gas-6\u2013mediated clearance of circulating microparticles in TBI mice and investigated the molecular interactions by which Gas-6 binds microparticles and macrophages to facilitate microparticle scavenging.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>We found that plasma levels of Gas-6 were significantly reduced in mice subjected to severe TBI. Exogenous Gas-6 given either preinjury or postinjury attenuated coagulopathy, protected the integrity of the cerebral and pulmonary endothelium, improved neurological recovery, and increased overall survival of TBI mice. Gas-6 increased the clearance of anionic phospholipid-expressing microparticles from circulation by coupling microparticles with macrophages and monocytes through the \u03b3-carboxyglutamate and the LG1 (laminin G-like domain 1), respectively, to facilitate phagocytosis of microparticles in the liver.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>These findings demonstrate the therapeutic potential of Gas-6 for TBI and potentially for other acute pathologies, in which microparticles initiate and propagate coagulation dysfunction and endothelial injuries.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/atvbaha.126.324955","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T09:00:23Z","timestamp":1786006823000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Gas-6 Scavenges Anionic Phospholipid-Expressing Microparticles and Mitigates TBI-Induced Endotheliopathy and Coagulopathy in Mice"],"prefix":"10.1161","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-7652-9069","authenticated-orcid":true,"given":"Hao","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Tianjin Neurological Institute, State Key Laboratory of Experimental Hematology (H.Z., T.M., X.Z., Y.Z., K.P., Z. Zhou, P.Z., L.T., C.L., X.R., Y. Liu, G.Y., Z. Zhao), Tianjin Medical University General Hospital, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4453-9687","authenticated-orcid":true,"given":"Yuyang","family":"Miao","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Key Laboratory of Post-Neuroinjury Neuro-Repair and Regeneration in the Central Nervous System, Ministry of Education, State Key Laboratory of Experimental Hematology, Tianjin Key Laboratory of Elderly Health, Tianjin Geriatrics Institute (Y.M.), Tianjin Medical University General Hospital, China."},{"name":"Laboratory of Molecular Ophthalmology, Department of Ophthalmology, Tianjin Medical University (Y.M.), Tianjin Medical University General Hospital, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianrui","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Tianjin Neurological Institute, State Key Laboratory of Experimental Hematology (H.Z., T.M., X.Z., Y.Z., K.P., Z. Zhou, P.Z., L.T., C.L., X.R., Y. Liu, G.Y., Z. Zhao), Tianjin Medical University General Hospital, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Tianjin Neurological Institute, State Key Laboratory of Experimental Hematology (H.Z., T.M., X.Z., Y.Z., K.P., Z. Zhou, P.Z., L.T., C.L., X.R., Y. Liu, G.Y., Z. Zhao), Tianjin Medical University General Hospital, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0098-1213","authenticated-orcid":true,"given":"Yuhua","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology &amp; Blood Diseases Hospital, Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Tianjin (Y.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2735-8626","authenticated-orcid":true,"given":"Yichi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Tianjin Neurological Institute, State Key Laboratory of Experimental Hematology (H.Z., T.M., X.Z., Y.Z., K.P., Z. Zhou, P.Z., L.T., C.L., X.R., Y. Liu, G.Y., Z. 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