Circulating levels of the angiogenesis mediators endoglin, HB-EGF, BMP-9 and FGF-2 in patients with severe sepsis and septic shock

Abstract

Purpose: Endothelial barrier dysfunction is a hallmark of sepsis, and is at least partially mediated by pathways that regulate endothelial barrier assembly during angiogenesis. Not surprisingly, increased levels of key angiogenic proteins such as VEGF-A and Angiopoietin-2 have been described in sepsis. The purpose of this study was to investigate if additional pathways that regulate endothelial barrier integrity during angiogenesis could also be involved in the host response of sepsis.

Material and methods: We evaluated circulating levels of four proteins involved in angiogenesis, not previously studied in sepsis, in a cohort of 50 patients with severe sepsis and septic shock.

Results: Circulating levels of BMP-9 and FGF-2 were similar in patients and healthy volunteers. In contrast, patients with septic shock presented 1.5-fold higher levels of endoglin (P=0.004), and 2-fold lower levels of Heparin-Binding EGF-like growth factor (HB-EGF) (P=0.002) when compared to healthy individuals. Of note, HB-EGF deficiency has been recently demonstrated to be detrimental to survival in a murine model of sepsis.

Conclusions: Endoglin and HB-EGF could be involved in the host response of sepsis. Additional studies are warrant to investigate their role as biomarker or therapeutic targets in sepsis.

Keywords: Angiogenesis; BMP-9; Endoglin; Endothelial barrier; FGF-2; HB-EGF; Sepsis.