{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T21:00:50Z","timestamp":1773262850640,"version":"3.50.1"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T00:00:00Z","timestamp":1724889600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T00:00:00Z","timestamp":1724889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000057","name":"NIGMS","doi-asserted-by":"crossref","award":["GM112806"],"award-info":[{"award-number":["GM112806"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"crossref","award":["HL154688"],"award-info":[{"award-number":["HL154688"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["ICMx"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Sepsis can lead to coagulopathy and microvascular thrombosis. Prior studies, including ours, reported an increased level of extracellular vimentin in blood derived from septic patients. Moreover, we identified the contribution of extracellular vimentin to fibrin formation and to the fibrin clot structure ex vivo in plasma from septic patients. Here, we tested the status of plasma vimentin and its impact on fibrin clots using our recently described swine model of methicillin-resistant Staphylococcus aureus (MRSA) sepsis-induced coagulopathy.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We employed ELISA, size-exclusion chromatography, vimentin antibodies, confocal microscopy, and turbidity assays on piglet plasma obtained at pre- and post-MRSA inoculation. Plasma vimentin level at 70\u00a0h post-MRSA inoculation was on average twofold higher compared to pre-infection (0\u00a0h) level in the same animal. Anti-vimentin antibody effectively reduced fibrin formation ex vivo and increased porosity in the fibrin clot structure generated from septic piglet plasma. In contrast to plasma at 0\u00a0h, the size-exclusion chromatography revealed that phosphorylated vimentin was in-complex with fibrinogen in septic piglet plasma.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Thus, our swine model of sepsis-induced coagulopathy, reproduced increased extracellular circulating vimentin and subsequent potentiation of fibrin formation, often observed in septic patient. These outcomes validate the use of large animal models to investigate the dysregulated host immune response to infection leading to coagulopathy, and to develop new therapies for sepsis-induced disseminated microvascular thrombosis.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s40635-024-00660-5","type":"journal-article","created":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T11:03:38Z","timestamp":1724929418000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Elevated level of extracellular vimentin is associated with an increased fibrin formation potential in sepsis: ex vivo swine study"],"prefix":"10.1186","volume":"12","author":[{"given":"Marina","family":"Martinez-Vargas","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arun","family":"Saini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Subhashree","family":"Pradhan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis","family":"Gardea","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Stoll","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inka C.","family":"Didelija","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. Vinod","family":"Vijayan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Trung C.","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel A.","family":"Cruz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,8,29]]},"reference":[{"key":"660_CR1","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1097\/ACO.0000000000000163","volume":"28","author":"J Simmons","year":"2015","unstructured":"Simmons J, Pittet JF (2015) The coagulopathy of acute sepsis. Curr Opin Anaesthesiol 28:227\u2013236","journal-title":"Curr Opin Anaesthesiol"},{"key":"660_CR2","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1055\/s-0039-1694995","volume":"46","author":"T Iba","year":"2020","unstructured":"Iba T, Levi M, Levy JH (2020) Sepsis-induced coagulopathy and disseminated intravascular coagulation. Semin Thromb Hemost 46:89\u201395","journal-title":"Semin Thromb Hemost"},{"key":"660_CR3","first-page":"1","volume":"5","author":"MP Fink","year":"2013","unstructured":"Fink MP (2013) Animal models of sepsis1. Virulence 5:1","journal-title":"Virulence"},{"key":"660_CR4","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1038\/nrd4368","volume":"13","author":"MP Fink","year":"2014","unstructured":"Fink MP, Warren HS (2014) Strategies to improve drug development for sepsis. Nat Rev Drug Discovery 13:741\u2013758","journal-title":"Nat Rev Drug Discovery"},{"key":"660_CR5","doi-asserted-by":"publisher","DOI":"10.1097\/CCE.0000000000000916","volume":"5","author":"TC Nguyen","year":"2023","unstructured":"Nguyen TC, Marini JC, Guillory B, Valladolid-Brown C, Martinez-Vargas M, Subramanyam D, Cohen D, Cirlos SC, Lam F, Stoll B, Didelija IC, Vonderohe C, Orellana R, Saini A, Pradhan S, Bashir D, Desai MS, Flores S, Virk M, Tcharmtchi H, Navaei A, Kaplan S, Lamberth L, Hulten KG, Scull BP, Allen CE, Akcan-Arikan A, Vijayan KV, Cruz MA (2023) Pediatric swine model of methicillin-resistant staphylococcus aureus sepsis-induced coagulopathy, disseminated microvascular thrombosis, and organ injuries. Crit Explorat 5:e0916","journal-title":"Crit Explorat"},{"key":"660_CR6","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.ijid.2022.05.018","volume":"121","author":"H Miao","year":"2022","unstructured":"Miao H, Cui Y, Lu Y, Sun T, Dou J, Ren Y, Wang C, Zhang Y (2022) Serum vimentin predicts mortality in pediatric severe sepsis: a prospective observational study. Int J Infect Dis 121:141\u2013147","journal-title":"Int J Infect Dis"},{"key":"660_CR7","doi-asserted-by":"publisher","first-page":"5747","DOI":"10.1038\/s41598-019-42287-7","volume":"9","author":"L Su","year":"2019","unstructured":"Su L, Pan P, Yan P, Long Y, Zhou X, Wang X, Zhou R, Wen B, Xie L, Liu D (2019) Role of vimentin in modulating immune cell apoptosis and inflammatory responses in sepsis. Sci Rep 9:5747","journal-title":"Sci Rep"},{"key":"660_CR8","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.thromres.2022.11.028","volume":"221","author":"M Martinez-Vargas","year":"2023","unstructured":"Martinez-Vargas M, Cebula A, Brubaker LS, Seshadri N, Lam FW, Loor M, Rosengart TK, Yee A, Rumbaut RE, Cruz MA (2023) A novel interaction between extracellular vimentin and fibrinogen in fibrin formation. Thromb Res 221:97\u2013104","journal-title":"Thromb Res"},{"key":"660_CR9","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1097\/CCM.0000000000005465","volume":"50","author":"LS Brubaker","year":"2022","unstructured":"Brubaker LS, Saini A, Nguyen TC, Martinez-Vargas M, Lam FW, Yao Q, Loor MM, Rosengart TK, Cruz MA (2022) Aberrant fibrin clot structure visualized ex vivo in critically Ill patients with severe acute respiratory syndrome coronavirus 2 infection. Crit Care Med 50:6","journal-title":"Crit Care Med"},{"key":"660_CR10","doi-asserted-by":"publisher","first-page":"1340","DOI":"10.1182\/bloodadvances.2020001500","volume":"4","author":"C Valladolid","year":"2020","unstructured":"Valladolid C, Martinez-Vargas M, Sekhar N, Lam F, Brown C, Palzkill T, Tischer A, Auton M, Vijayan KV, Rumbaut RE, Nguyen TC, Cruz MA (2020) Modulating the rate of fibrin formation and clot structure attenuates microvascular thrombosis in systemic inflammation. Blood Adv 4:1340\u20131349","journal-title":"Blood Adv"},{"key":"660_CR11","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1038\/328649a0","volume":"328","author":"M Inagaki","year":"1987","unstructured":"Inagaki M, Nishi Y, Nishizawa K, Matsuyama M, Sato C (1987) Site-specific phosphorylation induces disassembly of vimentin filaments in vitro. Nature 328:649\u2013652","journal-title":"Nature"},{"key":"660_CR12","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1242\/jcs.00906","volume":"117","author":"JE Eriksson","year":"2004","unstructured":"Eriksson JE, He T, Trejo-Skalli AV, H\u00e4rm\u00e4l\u00e4-Brask\u00e9n AS, Hellman J, Chou YH, Goldman RD (2004) Specific in vivo phosphorylation sites determine the assembly dynamics of vimentin intermediate filaments. J Cell Sci 117:919\u2013932","journal-title":"J Cell Sci"},{"key":"660_CR13","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2022.867796","volume":"9","author":"A Rutai","year":"2022","unstructured":"Rutai A, Zsikai B, Tallosy SP, Erces D, Bizanc L, Juhasz L, Poles MZ, Soki J, Baaity Z, Fejes R, Varga G, Foldesi I, Burian K, Szabo A, Boros M, Kaszaki J (2022) A porcine sepsis model with numerical scoring for early prediction of severity. Front Med (Lausanne) 9:867796","journal-title":"Front Med (Lausanne)"},{"key":"660_CR14","doi-asserted-by":"publisher","first-page":"11728","DOI":"10.1074\/jbc.273.19.11728","volume":"273","author":"H Goto","year":"1998","unstructured":"Goto H, Kosako H, Tanabe K, Yanagida M, Sakurai M, Amano M, Kaibuchi K, Inagaki M (1998) Phosphorylation of vimentin by Rho-associated kinase at a unique amino-terminal site that is specifically phosphorylated during cytokinesis. J Biol Chem 273:11728\u201311736","journal-title":"J Biol Chem"},{"key":"660_CR15","doi-asserted-by":"publisher","first-page":"L149","DOI":"10.1152\/ajplung.00100.2021","volume":"322","author":"L Wang","year":"2022","unstructured":"Wang L, Letsiou E, Wang H, Belvitch P, Meliton LN, Brown ME, Bandela M, Chen J, Garcia JGN, Dudek SM (2022) MRSA-induced endothelial permeability and acute lung injury are attenuated by FTY720 S-phosphonate. Am J Physiol Lung Cell Mol Physiol 322:L149-l161","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"660_CR16","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1038\/nrm3753","volume":"15","author":"NT Snider","year":"2014","unstructured":"Snider NT, Omary MB (2014) Post-translational modifications of intermediate filament proteins: mechanisms and functions. Nat Rev Mol Cell Biol 15:163\u2013177","journal-title":"Nat Rev Mol Cell Biol"},{"key":"660_CR17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/cvr\/cvad017","volume":"119","author":"M Zabczyk","year":"2023","unstructured":"Zabczyk M, Ariens RAS, Undas A (2023) Fibrin clot properties in cardiovascular disease: from basic mechanisms to clinical practice. Cardiovasc Res 119:1","journal-title":"Cardiovasc Res"},{"key":"660_CR18","first-page":"3","volume":"6","author":"M Wygrecka","year":"2021","unstructured":"Wygrecka M, Birnhuber A, Seeliger B, Michalick L, Pak O, Schultz A-S, Schramm F, Zacharias M, Gorkiewicz G, David S, Welte T, Schmidt JJ, Weissmann N, Schermuly RT, Barreto G, Schaefer L, Markart P, Brack MC, Hippenstiel S, Kurth F, Sander L, Witzenrath M, Kuebler W, Kwapiszewska G, Preissner KT (2021) Altered fibrin clot structure and dysregulated fibrinolysis contribute to thrombosis risk in severe COVID-19. Blood Adv 6:3","journal-title":"Blood Adv"},{"key":"660_CR19","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1055\/s-0039-1696944","volume":"46","author":"E Mihalko","year":"2020","unstructured":"Mihalko E, Brown AC (2020) Clot Structure and Implications for Bleeding and Thrombosis. Semin Thromb Hemost 46:96\u2013104","journal-title":"Semin Thromb Hemost"},{"key":"660_CR20","doi-asserted-by":"publisher","first-page":"1482","DOI":"10.1055\/s-0037-1614859","volume":"82","author":"JP Colle","year":"1999","unstructured":"Colle JP, Mishal Z, Lesty C, Mirshahi M, Peyne J, Baumelou A, Bensman A, Soria J, Soria C (1999) Abnormal fibrin clot architecture in nephrotic patients is related to hypofibrinolysis: influence of plasma biochemical modifications: a possible mechanism for the high thrombotic tendency? Thromb Haemost 82:1482\u20131489","journal-title":"Thromb Haemost"},{"key":"660_CR21","doi-asserted-by":"publisher","first-page":"24259","DOI":"10.1016\/S0021-9258(18)35759-4","volume":"267","author":"DA Gabriel","year":"1992","unstructured":"Gabriel DA, Muga K, Boothroyd EM (1992) The effect of fibrin structure on fibrinolysis. J Biol Chem 267:24259\u201324263","journal-title":"J Biol Chem"},{"key":"660_CR22","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1097\/HJH.0000000000001269","volume":"35","author":"K Jozwik-Plebanek","year":"2017","unstructured":"Jozwik-Plebanek K, Prejbisz A, Wypasek E, Pregowska-Chwala B, Hanus K, Kaszuba AM, Januszewicz M, Bielen P, Kabat M, Kruk M, Dobrowolski P, Klisiewicz A, Sliwinski P, Januszewicz A, Undas A (2017) Altered plasma fibrin clot properties in hypertensive patients with obstructive sleep apnoea are improved by continuous positive airway pressure treatment. J Hypertens 35:1035\u20131043","journal-title":"J Hypertens"},{"key":"660_CR23","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.ijcard.2022.11.026","volume":"373","author":"J Siudut","year":"2023","unstructured":"Siudut J, Pudlo J, Konieczynska M, Polak M, Jawien J, Undas A (2023) Therapy with high-dose statins reduces soluble P-selectin: the impact on plasma fibrin clot properties. Int J Cardiol 373:110\u2013117","journal-title":"Int J Cardiol"},{"key":"660_CR24","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1097\/ALN.0000000000003165","volume":"132","author":"KA Nellenbach","year":"2020","unstructured":"Nellenbach KA, Nandi S, Kyu A, Sivadanam S, Guzzetta NA, Brown AC (2020) Comparison of neonatal and adult fibrin clot properties between porcine and human plasma. Anesthesiology 132:1091\u20131101","journal-title":"Anesthesiology"},{"key":"660_CR25","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1016\/j.thromres.2011.03.013","volume":"128","author":"U Kessler","year":"2011","unstructured":"Kessler U, Grau T, Gronchi F, Berger S, Brandt S, Bracht H, Marcucci C, Zachariou Z, Jakob SM (2011) Comparison of porcine and human coagulation by thrombelastometry. Thromb Res 128:477\u2013482","journal-title":"Thromb Res"},{"key":"660_CR26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/MBC.0000000000000301","volume":"27","author":"V Karlaftis","year":"2016","unstructured":"Karlaftis V, Perera S, Monagle P, Ignjatovic V (2016) Importance of post-translational modifications on the function of key haemostatic proteins. Blood Coagulat Fibrinol 27:1\u20134","journal-title":"Blood Coagulat Fibrinol"}],"container-title":["Intensive Care Medicine Experimental"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40635-024-00660-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40635-024-00660-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40635-024-00660-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T11:11:07Z","timestamp":1724929867000},"score":1,"resource":{"primary":{"URL":"https:\/\/icm-experimental.springeropen.com\/articles\/10.1186\/s40635-024-00660-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,29]]},"references-count":26,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["660"],"URL":"https:\/\/doi.org\/10.1186\/s40635-024-00660-5","relation":{},"ISSN":["2197-425X"],"issn-type":[{"value":"2197-425X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,29]]},"assertion":[{"value":"7 June 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 August 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 August 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All animal procedures were reviewed and approved by the Baylor College of Medicine Animal Care and Use Committee (study number: AN-6148 Arginine Metabolism in Sepsis; approved May 1, 2014, to August 24, 2022).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"M.A. Cruz and T. Nguyen are members of the board of A2 Therapeutics, Inc.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"75"}}