Soluble Vascular Endothelial‐Cadherin Levels in Patients With Sepsis Treated With Direct Hemoperfusion With a Polymyxin B‐immobilized Fiber Column

Abstract

Capillary permeability is a tightly regulated feature of microcirculation in all organ beds; however, in sepsis this feature is fundamentally altered. Several molecules are investigated as associated factors with capillary permeability and vascular endothelial (VE)-cadherin internalization by vascular endothelial growth factor (VEGF)-induced signaling through VEGF receptors leads to increased vascular endothelial cell detachment and trans-endothelial permeability. We investigated serum soluble VE-cadherin levels in septic patients. An enzyme-linked immunoassay was used to measure serum soluble VE-cadherin levels in 47 septic patients treated by direct hemoperfusion with a polymyxin B-immobilized fiber column (DHP-PMX). The serum soluble VE-cadherin level of septic patients before PMX-DHP was 3424.1 ± 2033.0 ng/mL, which was significantly lower than that of the controls (5862.0 ± 1521.2 ng/mL; P < 0.0001). The time course of serum soluble VE-cadherin levels remained unchanged during PMX-DHP therapy. There was no significant difference in serum soluble VE-cadherin levels before PMX-DHP therapy between survivors and non-survivors, and there was no significant difference in those levels between the groups at any time after the initiation of PMX-DHP therapy. There was no correlation between soluble VE-cadherin levels and clinical data, except white blood cell count (r = -0.277, P = 0.0009). There was no correlation between soluble VE-cadherin levels and the levels of angiopoietin 1 and 2. In summary, the relationship between VE-cadherin and capillary permeability in sepsis could not be demonstrated. Soluble VE-cadherins are not reflected in the balance between intercellular junction plasticity and integrity, but VE-cadherin stabilization by its phosphorylation or internalization may be associated with capillary permeability.

Vascular endothelial cadherin shedding is more severe in sepsis patients with severe acute kidney injury

“…Doulgere et al reported plasma sVE-cadherin levels were still elevated when serum creatinine levels decreased or were close to normal range in patients with hemolytic uremic syndrome due to Shiga toxin 2 producing Escherichia coli infection (STEC-HUS) [41]. Ebihara et al reported that there was no difference in plasma sVE-cadherin levels before and after renal replacement therapy in sepsis patients [42]. Whether elevated levels of sVE-cadherin are in part due to impaired clearance in the setting of other organ dysfunction needs to be further investigated.…”

Plasma concentration of selected biochemical markers of endothelial dysfunction in women with various severity of chronic venous insufficiency (CVI)—A pilot study

“…coli strain (STEC) and with the haemolytic ureamic syndrome (HUS), a complication caused by this bacteria and occurs via endothelial cell damage [ 61 ]. The study by Ebihara et al shows that sepsis, a pathology accompanied by massive endothelial disruption and damage, is associated with decreased sVE-cadherin level [ 62 ]. Ostrowski et al, who investigated the markers of endothelial damage in patients with severe sepsis, obtained results identical to ours, namely a fall in sVE-cadherin concentration accompanied by the rise in sTM level [ 63 ].…”

Soluble plasma VE-cadherin concentrations are elevated in patients with STEC infection and haemolytic uraemic syndrome: a case–control study

“…Kidney endothelial cells, similarly to several other renal cell types, have receptors for stx2 and are damaged by the toxin in vitro. 25 Zhang et al 26 and Ebihara et al 27 described the association between severe sepsis and soluble VE-cadherin concentrations in serum.…”