Endocan (endothelial cell-specific molecule-1) as a pertinent biomarker of endothelial dysfunction in sepsis

Introduction

One of the main players in the severity of sepsis is the endothelium integrity. Endocan, also called endothelial cell-specific molecule-1 (ESM-1), was shown to be preferentially expressed in lung vasculature. Structurally, endocan/ESM-1 is a 50 kDa proteoglycan that can interact with ICAM-1 and LFA-1 integrins and consequently prevents inflammatory events. In an experimental rat endotoxemic shock model, we previously showed that a decrease in the leukocyte-endothelial cell contacts (induced by drugs) is clearly linked to an increase of blood endocan levels. Blood levels of endocan/ESM-1 were also shown to be associated with the severity and evolution of septic states in preliminary studies.

Methods

We have designed a prospective observational larger clinical study with 125 septic patients recruited to assess endocan/ESM-1 blood levels concomitantly with a comparison with survival at D10, severity score (SAPS II) at D2 and D7, and other biomarkers such as procalcitonin, CRP, and interleukins. ICU patients were followed over a 28-day period. Time course kinetics of serum endocan/ESM-1 at D0, D2, and D7 were performed using an ELISA assay (EndoMark H1; Lunginnov).

Results

Our preliminary results for 39 patients showed that endocan/ESM-1 blood levels were increased at ICU admission in patients with poor prognosis (severe sepsis and septic shock). The monitoring of plasma endocan/ESM-1 at D2 and D7 revealed sustained elevated endocan levels in patients deceased within D10 (n = 12). By contrast, the endocan levels fall down as early as D2 in patients who survived at D10 (n = 27). Among the other molecules evaluated in this study, only anti-inflammatory IL-10 presented similar variations to endocan/ESM-1. These results suggest that both endocan/ESM-1 and IL-10 may have potent predictive values for patient follow up.

Conclusions

We have demonstrated that a simple, accurate, and blood-based biomarker such as endocan/ESM-1 (EndoMark H1; Lunginnov) could assess the initial severity and closely follow the inflammatory events and endothelial dysfunction in patients, and therefore would be hugely helpful for clinicians to predict outcome and to select more appropriate therapeutic strategies.