title: Airway concentrations of angiopoietin-1 and endostatin in ventilated extremely premature infants are decreased after funisitis and unbalanced with bronchopulmonary dysplasia/death.
abstract: A systemic inflammatory response of the fetus, reflected by histologic funisitis, is a risk factor for bronchopulmonary dysplasia (BPD). Impaired pulmonary angiogenesis accompanied by simplification and rarification of alveoli is a histologic hallmark of BPD. Angiopoietin-1 mediates vascular development, maturation, and stabilization. Endostatin mainly acts as an angiostatic factor. We hypothesized that funisitis was associated with changes of endostatin and angiopoietin-1 concentrations in the airways and that an imbalance between the factors might be associated with BPD or death. We measured concentrations of angiopoietin-1 and endostatin by enzyme-linked immunosorbent assay in tracheobronchial aspirate fluid samples of 42 ventilated preterm infants during postnatal days 1 through 15. The secretory component for IgA served as reference protein. A standardized histologic examination was used to distinguish three groups: chorioamnionitis, funisitis, and controls without inflammation. Concentrations of the mediators steadily decreased. Funisitis was associated with lower concentrations of both proteins, which might impair their physiologic activities in pulmonary angiogenesis. An increase of the ratio angiopoietin-1/endostatin until day 7 of life indicated a shift of the mediators potentially favoring angiogenesis. However, infants, who developed BPD or died, had a decreased ratio on days 1, 3, and 15, suggesting an imbalance toward inhibition of pulmonary angiogenesis.
authors.affiliation: University Children's Hospital, University Hospital Würzburg, Würzburg 97080, 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: Natalia
authors.initials: N
authors.lastname: Kawczyńska-Leda
authors.forename: Maria
authors.initials: M
authors.lastname: Chmielnicka-Kopaczyk
authors.forename: Alexander
authors.initials: A
authors.lastname: Marx
authors.forename: Johannes
authors.initials: J
authors.lastname: Wirbelauer
authors.forename: Marta
authors.initials: M
authors.lastname: Szymankiewicz
authors.forename: Christian P
authors.initials: CP
authors.lastname: Speer
mesh_terms: D042683:Angiopoietin-1 / Q000378:metabolism*; D001997:Bronchopulmonary Dysplasia / Q000209:etiology / Q000378:metabolism* / Q000401:mortality / Q000503:physiopathology; D002821:Chorioamnionitis / Q000378:metabolism* / Q000401:mortality / Q000503:physiopathology; D015536:Down-Regulation; D043169:Endostatins / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005865:Gestational Age; D006801:Humans; D007071:Immunoglobulin A, Secretory / Q000378:metabolism; D007231:Infant, Newborn; D007234:Infant, Premature; D007363:Intensive Care Units, Neonatal; D008168:Lung / Q000098:blood supply / Q000378:metabolism*; D008297:Male; D018919:Neovascularization, Physiologic; D011247:Pregnancy; D011446:Prospective Studies; D012121:Respiration, Artificial; D012720:Severity of Illness Index; D013997:Time Factors
chemical_list: C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D043169:Endostatins; D007071:Immunoglobulin A, Secretory