Publication Date
8-29-2024
Journal
Intensive Care Medicine Experimental
DOI
10.1186/s40635-024-00660-5
PMID
39207603
PMCID
PMC11362409
PubMedCentral® Posted Date
8-29-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Large animal model, Sepsis, Coagulopathy, Fibrin, Vimentin
Abstract
BACKGROUND: 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.
RESULTS: 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 h post-MRSA inoculation was on average twofold higher compared to pre-infection (0 h) 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 h, the size-exclusion chromatography revealed that phosphorylated vimentin was in-complex with fibrinogen in septic piglet plasma.
CONCLUSIONS: 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.
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