Angiopoietin-2 correlates with pulmonary capillary permeability and disease severity in critically ill patients

Introduction

It has previously been shown that angiopoietin-1 (Ang1) protects the adult vasculature against plasma leakage, whereas Ang2 and VEGF destabilize the vascular endothelium resulting in vascular leakage. Consequently they might be involved in the pathophysiology of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) in sepsis patients. We hypothesized that plasma Ang2 levels are associated with pulmonary capillary protein permeability, the lung injury score (LIS), length of stay on the ICU, the APACHE II score and survival in septic patients with ALI or ARDS.

Methods

A prospective observational study was performed in an ICU of an university hospital on 112 patients: 38 after elective cardiac surgery, 26 after major vascular surgery, 24 with sepsis and 24 with trauma. Plasma levels of Ang1, Ang2 and VEGF were measured and a mobile probe system was used to measure the pulmonary leak index (PLI) (that is, the transvascular transport rate of gallium-67-radiolabeled transferrin).

Results

Plasma levels of Ang2 and the PLI were significantly higher in patients with sepsis compared with other patient groups. In the sepsis group, a positive linear correlation was observed between plasma levels of Ang2 and length of stay on the ICU (r_s = 0.509, P < 0.05) as index for disease severity. For all patients together, Ang2 had a positive linear correlation with PLI (r_s = 0.374, P < 0.01), LIS (r_s = 0.489, P < 0.01) and APACHE II score (r_s = 0.287, P < 0.01). Furthermore, Ang2 was significantly increased in nonsurvivors. Plasma Ang1 levels did not differ between groups. VEGF levels were undetectable in the plasma of the majority of patients.

Conclusion

Our results suggest that Ang2 is a mediator of pulmonary capillary permeability and a marker of disease severity in critically ill patients. Furthermore, the plasma levels of Ang2 and the ratio between Ang1 and Ang2 are more important in pulmonary capillary permeability and disease severity than absolute levels of Ang1 and VEGF.