title: Airway angiopoietin-2 in ventilated very preterm infants: association with prenatal factors and neonatal outcome.
abstract: 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.
authors.affiliation: University Children's Hospital, University of Würzburg, Germany. thomas_w@klinik.uni-wuerzburg.de
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Thomas
authors.forename: Silvia
authors.initials: S
authors.lastname: Seidenspinner
authors.forename: Boris W
authors.initials: BW
authors.lastname: Kramer
authors.forename: Johannes
authors.initials: J
authors.lastname: Wirbelauer
authors.forename: Natalia
authors.initials: N
authors.lastname: Kawczyńska-Leda
authors.forename: Marta
authors.initials: M
authors.lastname: Szymankiewicz
authors.forename: Christian P
authors.initials: CP
authors.lastname: Speer
mesh_terms: D042683:Angiopoietin-1 / Q000097:blood; D042702:Angiopoietin-2 / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D001997:Bronchopulmonary Dysplasia / Q000097:blood / Q000378:metabolism / Q000401:mortality; D002821:Chorioamnionitis / Q000378:metabolism; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000378:metabolism / Q000401:mortality; D019102:Infant, Very Low Birth Weight; D008297:Male; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism / Q000401:mortality; D047928:Premature Birth / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D042683:Angiopoietin-1; D042702:Angiopoietin-2