Disrupted pulmonary vasculature and decreased vascular endothelial growth factor, Flt-1, and TIE-2 in human infants dying with bronchopulmonary dysplasia

Am J Respir Crit Care Med. 2001 Nov 15;164(10 Pt 1):1971-80. doi: 10.1164/ajrccm.164.10.2101140.


An abnormal pulmonary vasculature may be an important component of bronchopulmonary dysplasia (BPD). We examined human infant lung for the endothelial cell marker PECAM-1 and for angiogenic factors and their receptors. Lung specimens were collected prospectively at approximately 6 h after death. The right middle lobe was inflation fixed and part of the right lower lobe was flash frozen. We compared lungs from infants dying with BPD (n = 5) with lungs from infants dying from nonpulmonary causes (n = 5). The BPD group was significantly more premature and had more days of ventilator and supplemental oxygen support, but died at a postconceptional age similar to control infants. PECAM-1 protein and mRNA were decreased in the BPD group. PECAM-1 immunohistochemistry showed the BPD group had decreased staining intensity and abnormal distribution of alveolar capillaries. The dysmorphic capillaries were frequently in the interior of thickened alveolar septa. The BPD group had decreased vascular endothelial growth factor (VEGF) mRNA and decreased VEGF immunostaining, compared with infants without BPD. Messages for the angiogenic receptors Flt-1 and TIE-2 were decreased in the BPD group. We conclude that infants dying with BPD have abnormal alveolar microvessels and that disordered expression of angiogenic growth factors and their receptors may contribute to these abnormalities.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Age Factors
  • Autopsy
  • Biomarkers / analysis
  • Birth Weight
  • Bronchopulmonary Dysplasia / embryology
  • Bronchopulmonary Dysplasia / etiology*
  • Bronchopulmonary Dysplasia / mortality
  • Bronchopulmonary Dysplasia / pathology*
  • Capillaries / abnormalities*
  • Capillaries / embryology
  • Capillaries / pathology*
  • Case-Control Studies
  • Cause of Death
  • Endothelial Growth Factors / analysis*
  • Extracellular Matrix Proteins / analysis*
  • Gestational Age
  • Humans
  • Immunohistochemistry
  • Infant, Newborn
  • Lymphokines / analysis*
  • Neovascularization, Physiologic / physiology
  • Platelet Endothelial Cell Adhesion Molecule-1 / analysis*
  • Prospective Studies
  • Pulmonary Alveoli / blood supply*
  • Receptor Protein-Tyrosine Kinases / analysis*
  • Receptor, TIE-2
  • Respiration, Artificial / adverse effects
  • Risk Factors
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor Receptor-1
  • Vascular Endothelial Growth Factors


  • Biomarkers
  • Endothelial Growth Factors
  • Extracellular Matrix Proteins
  • Lymphokines
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • FLT1 protein, human
  • Receptor Protein-Tyrosine Kinases
  • Receptor, TIE-2
  • Vascular Endothelial Growth Factor Receptor-1