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.

Keywords: Direct hemoperfusion; Polymyxin B immobilized fiber column; Sepsis; Soluble vascular endothelial-cadherin.