Published online August 1, 2008
PEDIATRICS Vol. 122 No. 2 August 2008, pp. 340-346 (doi:10.1542/peds.2007-1941)

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ARTICLE

Placental Growth Factor and Vascular Endothelial Growth Factor Receptor-2 in Human Lung Development

Joakim Janér, MD^a, Sture Andersson, MD, PhD^a, Caj Haglund, MD, PhD^b, Riitta Karikoski, MD^c and Patrik Lassus, MD, PhD^d

^a Hospital for Children and Adolescents
^b Departments of Surgery
^c Pathology
^d Plastic Surgery, University of Helsinki, Helsinki, Finland

OBJECTIVE. We examined the pulmonary expression of 2 proangiogenic factors, namely, placental growth factor and vascular endothelial growth factor receptor-2, during lung development and acute and chronic lung injury in newborn infants.

METHODS. Six groups were included in an immunohistochemical study of placental growth factor and vascular endothelial growth factor receptor-2, that is, 9 fetuses, 4 preterm and 8 term infants without lung injury who died soon after birth, 5 preterm infants with respiratory distress syndrome of <2 days and 7 with respiratory distress syndrome of >10 days, and 6 with bronchopulmonary dysplasia. Placental growth factor concentrations in tracheal aspirate fluid were measured in 70 samples from 20 preterm infants during the first postnatal week.

RESULTS. In immunohistochemical analyses, placental growth factor staining was seen in bronchial epithelium and macrophages in all groups. Distal airway epithelium positivity was observed mostly in fetuses and in preterm infants who died soon after birth. Vascular endothelial growth factor receptor-2 staining was seen in vascular endothelium in all groups and also in lymphatic endothelium in fetuses. Vascular endothelial growth factor receptor-2 staining in arterial endothelium was associated with higher and staining in venous endothelium with lower gestational age. In capillaries, less vascular endothelial growth factor receptor-2 staining was seen in bronchopulmonary dysplasia. The mean placental growth factor protein concentration in tracheal aspirate fluid during the first postnatal week was 0.64 ± 0.42 pg/mL per IgA-secretory component unit. Concentrations during the first postnatal week were stable. Lower placental growth factor concentrations correlated with chorioamnionitis and lactosyl ceramide positivity.

CONCLUSIONS. The vascular endothelial growth factor receptor-2 staining pattern seems to reflect ongoing differentiation and activity of different endothelia. Lower vascular endothelial growth factor receptor-2 expression in capillary endothelium in bronchopulmonary dysplasia might be a reflection of the dysregulation of vascular development that is characteristic of bronchopulmonary dysplasia.

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Key Words: lung development • neonatal • respiratory • bronchopulmonary dysplasia

Abbreviations: BW—birth weight • BPD—bronchopulmonary dysplasia • GA—gestational age • PlGF—placental growth factor • RDS—respiratory distress syndrome • TAF—tracheal aspirate fluid • VEGF—vascular endothelial growth factor • VEGFR—vascular endothelial growth factor receptor • IgA-SC—secretory component of IgA

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Accepted Dec 15, 2007.

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