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.