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Progressive endothelial cell damage in correlation with sepsis severity. Defibrotide as a contender
Author(s) -
Fernández Sara,
Palomo Marta,
Molina Patricia,
DíazRicart Maribel,
Escolar Ginés,
Téllez Adrián,
Seguí Ferran,
Ventosa Helena,
TorramadeMoix Sergi,
Rovira Montserrat,
Carreras Enric,
Nicolás Josep M.,
Castro Pedro
Publication year - 2021
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.15343
Subject(s) - sepsis , von willebrand factor , medicine , endothelium , septic shock , endothelial dysfunction , immunology , inflammation , endothelial stem cell , proinflammatory cytokine , defibrotide , pathophysiology , cell adhesion molecule , thrombogenicity , platelet , endothelial activation , biology , in vitro , biochemistry , transplantation , hematopoietic stem cell transplantation
Background The vascular endothelium plays a key role in sepsis pathophysiology and the associated organ dysfunction. Methods We evaluated endothelial function in an experimental in vitro model of sepsis, using endothelial cells grown in the presence of serum from patients with septic syndromes (sepsis, severe sepsis, and septic shock), noninfectious systemic inflammatory response syndrome (NI‐SIRS) and healthy volunteers. Experiments were performed in the absence and presence of defibrotide (DF) (100 µg/ml) to evaluate its potential protective effect. Results After exposure to patients' sera, there was a progressive endothelial cell activation in correlation with sepsis severity, with a proinflammatory and prothrombotic phenotype, exhibiting significantly increased expression of adhesion receptors at the surface (intercellular adhesion molecule‐1, p < .05 and vascular cell adhesion molecule‐1, p < .05); higher production and release to the extracellular matrix (ECM) of von Willebrand factor ( p < .001); augmented thrombogenicity of the ECM toward platelets ( p < .001); and increased phosphorylation of intracellular p38MAPK. DF prevented these changes in all groups. Conclusions Markers of endothelial damage increased progressively in association with the severity of septic syndromes. The endothelium is therefore an important therapeutic target to prevent complications of sepsis. DF shows promising potential to modulate the endothelial damage associated with sepsis and may constitute a pharmacological tool to decrease its sequelae including multiorgan failure.