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High-density lipoprotein (HDL) exhibits antithrombotic activity, regulating coagulation in vascular endothelial cells. Sepsis induces the release of several proinflammatory molecules, including reactive oxygen species, which lead to an increase in oxidative stress in blood vessels. Thus, circulating lipoproteins, such as HDL, are oxidized to oxHDL, which promotes hemostatic dysfunction, acquiring prothrombotic properties linked to the severity of organ failure in septic-shock patients (SSP). However, a rigorous and comprehensive investigation demonstrating that oxHDL is associated with a coagulopathy-associated deleterious outcome of SSP, has not been reported. Thus, we investigated the participation of plasma oxHDL in coagulopathy-associated sepsis pathogenesis and elucidated the underlying molecular mechanism. A prospective study was conducted on 42 patients admitted to intensive care units, (26 SSP and 16 non-SSP) and 39 healthy volunteers. We found that an increased plasma oxHDL level in SSP was associated with a prothrombotic phenotype, increased mortality and elevated risk of death, which predicts mortality in SSP. The underlying mechanism indicates that oxHDL triggers an endothelial protein expression reprogramming of coagulation factors and procoagulant adhesion proteins, to produce a prothrombotic environment, mainly mediated by the endothelial LOX-1 receptor. Our study demonstrates that an increased plasma oxHDL level is associated with coagulopathy in SSP through a mechanism involving the endothelial LOX-1 receptor and endothelial protein expression regulation. Therefore, the plasma oxHDL level plays a role in the molecular mechanism associated with increased mortality in SSP.<\/jats:p>","DOI":"10.3390\/antiox12030543","type":"journal-article","created":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T03:59:16Z","timestamp":1677038356000},"page":"543","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Sepsis-Induced Coagulopathy Phenotype Induced by Oxidized High-Density Lipoprotein Associated with Increased Mortality in Septic-Shock Patients"],"prefix":"10.3390","volume":"12","author":[{"given":"Yolanda","family":"Prado","sequence":"first","affiliation":[{"name":"Laboratory of Integrative Physiopathology, Faculty of Life Science, Universidad Andres Bello, Santiago 8370186, Chile"},{"name":"Millennium Institute on Immunology and Immunotherapy, Santiago 8331150, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Tapia","sequence":"additional","affiliation":[{"name":"Unidad de Paciente Cr\u00edtico Adulto, Hospital Cl\u00ednico La Florida, La Florida, Santiago 8242238, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe","family":"Eltit","sequence":"additional","affiliation":[{"name":"Department of Urologic Sciences, University of British Columbia, Vancouver, BC V5Z 1M9, Canada"},{"name":"Vancouver Prostate Centre, Vancouver, BC V6H 3Z6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian","family":"Reyes-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Fish Immunology Laboratory, Faculty of Life Sciences, Universidad Andr\u00e9s Bello, Santiago 8370186, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen G.","family":"Feij\u00f3o","sequence":"additional","affiliation":[{"name":"Fish Immunology Laboratory, Faculty of Life Sciences, Universidad Andr\u00e9s Bello, Santiago 8370186, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4014-4474","authenticated-orcid":false,"given":"Felipe M.","family":"Llancalahuen","sequence":"additional","affiliation":[{"name":"Laboratory of Integrative Physiopathology, Faculty of Life Science, Universidad Andres Bello, Santiago 8370186, Chile"},{"name":"Millennium Institute on Immunology and Immunotherapy, Santiago 8331150, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia A.","family":"Riedel","sequence":"additional","affiliation":[{"name":"Millennium Institute on Immunology and Immunotherapy, Santiago 8331150, Chile"},{"name":"Laboratory of Endocrinology-Immunology, Faculty of Life Sciences, Universidad Andr\u00e9s Bello, Santiago 8370186, 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Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2653-9798","authenticated-orcid":false,"given":"Felipe","family":"Simon","sequence":"additional","affiliation":[{"name":"Laboratory of Integrative Physiopathology, Faculty of Life Science, Universidad Andres Bello, Santiago 8370186, Chile"},{"name":"Millennium Institute on Immunology and Immunotherapy, Santiago 8331150, Chile"},{"name":"Millennium Nucleus of Ion Channel-Associated Diseases (MiNICAD), Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1001\/jama.2016.0288","article-title":"Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock 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