Does low angiopoietin-1 predict adverse outcome in sepsis?

Abstract

Endothelial injury has emerged as a crucial early event in the pathogenesis of microcirculatory dysfunction, capillary leakage and multiorgan dysfunction syndrome. The endothelial-specific angiopoietin (Ang)/Tie2 ligand-receptor system has been identified recently as a nonredundant regulator of endothelial responsiveness. Ang-1 is a Tie2 agonist and promotes endothelial stabilization and quiescence, whereas Ang-2 is a Tie2 antagonist and promotes endothelial activation, destabilization, and inflammation. While the mediator function of both Ang-1 and Ang-2 has been well established in preclinical research, only Ang-2 has been identified as a clinically useful biomarker in the critical care arena. In the previous issue of Critical Care, Mankhambo and colleagues report on angiogenic factors in Malawian children with severe bacterial infection. Among those children, diminished levels of the vessel-protective factor Ang-1 remained a significant predictor of outcome after multivariate adjustment. Whether low Ang-1 represents an important risk factor of adverse outcome in critically ill adults remains to be seen.

Figure 1

Schematic model of circulating levels of angiogenic factors in Malawian children with severe infection. Schematic model of the main findings for circulating levels of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), angiopoietin (Ang)-1 and Ang-2 in Malawian children with severe infection from the study by Mankhambo and colleagues [1]. CI, confidence interval; OR, odds ratio.