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Impaired Lung Vascular Endothelial Growth Factor in Extremely Premature Baboons Developing Bronchopulmonary Dysplasia/Chronic Lung Disease
  1. Francis Tambunting,
  2. Kay D. A. Beharry,
  3. Joshua Waltzman,
  4. Houchang D. Modanlou
  1. From the Division of Neonatal-Perinatal Medicine (F.T., K.D.A.B., H.D.M.), Department of Pediatrics, University of California, Irvine Medical Center, Orange, CA; and Miller Children's Hospital (F.T., J.W.), Long Beach, CA. Presented in part at the 2004 Western Society for Pediatric Research Annual Meeting, Carmel, CA, and the 2004 Pediatric Academic Societies-Society for Pediatric Research Annual Meeting, San Francisco, CA.
  1. Address correspondence to: Dr. Houchang D. Modanlou, Pediatrics and Obstetrics/Gynecology, University of California, Irvine, Chief, Division of Neonatology, Director, Neonatal-Perinatal Medicine, Fellowship Training Program, University of California Irvine Medical Center, 101 The City Drive South, Building #56, Suite 600, Orange, CA 92868; tel: 714-456-6933; fax: 714-456-7658; e-mail: modanlou{at}


Background Preterm infants exposed to O2 with mechanical ventilation often develop bronchopulmonary dysplasia (BPD), a form of chronic lung disease (CLD). The pathogenesis of BPD/CLD involves dysmorphic microvasculature and disrupted alveolarization. This may be due to impaired vascular endothelial growth factor (VEGF) and VEGF receptor expression.

Methods To examine the ontogeny of VEGF and VEGF receptors in baboon lungs from 125 to 185 (term) days gestation and to determine whether exposure to O2 and mechanical ventilation alter these ontogenic profiles, we examined lung specimens from three O2-exposed groups: (1) animals delivered at 125 days gestation and exposed to O2 for 14 days as needed; (2) animals delivered at 140 days gestation and exposed to O2 for 10 days as needed; and (3) animals delivered at 140 days gestation and exposed to 100% O2 for 10 days. Lungs from gestational age-matched controls were also examined at 125, 140, 160, 175, and 185 (term) days.

Results VEGF189 was the most abundant splice variant in the lungs at all stages of development. Extremely premature baboons developing BPD/CLD had higher lung VEGF121 messenger ribonucleic acid (mRNA) expression. However, transcripts for VEGF189, VEGF165, and VEGF receptors (Fms-like tyrosine kinase-1 [Flt-1], kinase-insert domain receptor [KDR]/fetal liver kinase-1 [Flk-1], and neuropilin 1) were suppressed in the BPD models.

Conclusions We conclude that impaired VEGF and VEGF receptor mRNA expression in lungs from extremely premature baboons developing BPD/CLD may contribute to dysmorphic microvasculature and disrupted alveolarization.

Key Words
  • bronchopulmonary dysplasia
  • chronic lung disease
  • vascular endothelial growth factor

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