Airway angiopoietin-2 in ventilated very preterm infants: association with prenatal factors and neonatal outcome

Objective Pulmonary angiogenesis is a prerequisite for lung development. Angiopoietin-2 (Ang2) destabilizes endothelial cells through its endothelial receptor TIE-2, enabling vascular sprouting. Ang1 stabilizes new blood vessels. Soluble TIE-2 (sTIE-2) modulates these effects. We hypothesized that histological funisitis is associated with alterations of Ang2 in airways and of the systemic angiopoietin-TIE-2 homeostasis in very low birth weight (VLBW) infants, contributing to pulmonary morbidity and mortality. Methods We measured Ang2 in tracheobronchial aspirate fluid (TAF) of 42 VLBW <30 weeks of gestation from day 1 through 15 and Ang1, Ang2, and sTIE-2 in umbilical cord serum of 28 infants by enzyme-linked immunosorbent assay. Histological examination distinguished three groups: funisitis, chorioamnionitis, and controls. Results Funisitis was associated with lower Ang2 values in TAF but not with changes of Ang1, Ang2, and sTIE-2 in umbilical cord serum. Infants who developed bronchopulmonary dysplasia (BPD) or died had a persistently decreased ratio of previously measured Ang1 to Ang2 in TAF on days 1–5 and increased cord serum concentrations of sTIE-2. Moderate BPD/death was associated with an increase of Ang2 in TAF on day 10 and decreased Ang1/Ang2 ratio from day 3–15. Small for gestational age (SGA) infants had increased Ang2 in TAF on day 1–7 and a lower Ang1/Ang2 ratio on days 5–7. Conclusions The predominance of Ang2 in airway fluid of infants with BPD/death and SGA infants suggests a link between disrupted placental and fetal pulmonary angiogenesis. Histological funisitis with reduced Ang2 in TAF was of minor relevance for outcome in our cohort. Pediatr. Pulmonol. 2011; 46:777–784. © 2011 Wiley-Liss, Inc.