A Novel Interaction Between Extracellular Vimentin and Fibrinogen in Fibrin Formation

Authors

Marina Martinez-Vargas
Adrian Cebula
Lisa S Brubaker
Nitin Seshadri
Fong W Lam
Michele Loor
Todd K Rosengart
Andrew Yee
Rolando E Rumbaut
Miguel A Cruz

Publication Date

1-1-2023

Journal

Thrombosis Research

DOI

10.1016/j.thromres.2022.11.028

PMID

36495717

PMCID

PMC9726209

PubMedCentral® Posted Date

12-7-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Humans, COVID-19, Critical Illness, Fibrin, Fibrinogen, Hemostatics, Inflammation, Thrombosis, Vimentin, Extracellular Space, Vimentin, Coagulopathy, Systemic inflammation, Fibrinogen, sepsis, COVID-19

Abstract

INTRODUCTION: Thrombosis is frequently manifested in critically ill patients with systemic inflammation, including sepsis and COVID-19. The coagulopathy in systemic inflammation is often associated with increased levels of fibrinogen and D-dimer. Because elevated levels of vimentin have been detected in sepsis, we sought to investigate the relationship between vimentin and the increased fibrin formation potential observed in these patients.

MATERIALS AND METHODS: This hypothesis was examined by using recombinant human vimentin, anti-vimentin antibodies, plasma derived from healthy and critically ill patients, confocal microscopy, co-immunoprecipitation assays, and size exclusion chromatography.

RESULTS: The level of vimentin in plasma derived from critically ill subjects with systemic inflammation was on average two-fold higher than that of healthy volunteers. We determined that vimentin directly interacts with fibrinogen and enhances fibrin formation. Anti-vimentin antibody effectively blocked fibrin formation ex vivo and caused changes in the fibrin structure in plasma. Additionally, confocal imaging demonstrated plasma vimentin enmeshed in the fibrin fibrils. Size exclusion chromatography column and co-immunoprecipitation assays demonstrated a direct interaction between extracellular vimentin and fibrinogen in plasma from critically ill patients but not in healthy plasma.

CONCLUSIONS: The results describe that extracellular vimentin engages fibrinogen in fibrin formation. In addition, the data suggest that elevated levels of an apparent aberrant extracellular vimentin potentiate fibrin clot formation in critically ill patients with systemic inflammation; consistent with the notion that plasma vimentin contributes to the pathogenesis of thrombosis.

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