Pulmonary vascular endothelial growth factor and Flt-1 in fetuses, in acute and chronic lung disease, and in persistent pulmonary hypertension of the newborn

Am J Respir Crit Care Med. 2001 Nov 15;164(10 Pt 1):1981-7. doi: 10.1164/ajrccm.164.10.2012036.


Respiratory distress syndrome (RDS) and development of bronchopulmonary dysplasia (BPD) are characterized by endothelial cell damage. Persistent pulmonary hypertension of the newborn (PPHN) is a disorder that alters the pulmonary microvasculature. Immunohistochemistry for VEGFA(165), an endothelial cell mitogen, and its receptor Flt-1, was performed on lung tissues from autopsies from four fetuses, three preterm infants, four term infants without primary lung disease, four infants with BPD, and four infants with PPHN. VEGF was measured in tracheal aspirates from 31 preterm infants, 5 intubated term infants without primary lung injury, and 12 infants with PPHN during the first 10 postnatal days, and from 8 infants with BPD. Immunohistochemistry for VEGF and Flt-1 was similar in fetuses, preterm infants, and term infants: for VEGF mostly in bronchial epithelium and alveolar macrophages, and for Flt-1 mostly in vascular endothelial cells and bronchial epithelial cells. In patients with BPD, and PPHN, staining for VEGF and Flt-1 appeared also in Type II pneumocytes. Preterm infants with more severe RDS had lower VEGF than those who recovered. The persistent expression of VEGF and Flt-1 during the fetal and neonatal period supports a physiological role for VEGF in human lung development. The lower pulmonary VEGF in preterm infants with more severe RDS may contribute to the pathophysiology of the acute lung injury. In BPD, the expression of VEGF in alveolar epithelium may represent a compensatory increase after the acute phase of the lung disease. In PPHN, that more cell types express VEGF and Flt-1, and the tendency toward a higher concentration of pulmonary VEGF may represent enhanced production of VEGF in response to impaired endothelial function.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Analysis of Variance
  • Autopsy
  • Bronchopulmonary Dysplasia / blood
  • Bronchopulmonary Dysplasia / pathology*
  • Case-Control Studies
  • Chronic Disease
  • Endothelial Growth Factors / analysis*
  • Endothelial Growth Factors / physiology
  • Extracellular Matrix Proteins / analysis*
  • Extracellular Matrix Proteins / physiology
  • Female
  • Fetus / pathology*
  • Humans
  • Immunohistochemistry
  • Infant, Newborn* / blood
  • Infant, Premature* / blood
  • Lung / chemistry*
  • Lung / cytology
  • Lung / embryology
  • Lymphokines / analysis*
  • Lymphokines / physiology
  • Male
  • Persistent Fetal Circulation Syndrome / blood
  • Persistent Fetal Circulation Syndrome / pathology*
  • Pulmonary Alveoli / chemistry
  • Pulmonary Alveoli / cytology
  • Pulmonary Alveoli / embryology
  • Respiratory Distress Syndrome, Newborn / blood
  • Respiratory Distress Syndrome, Newborn / pathology*
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor Receptor-1
  • Vascular Endothelial Growth Factors


  • Endothelial Growth Factors
  • Extracellular Matrix Proteins
  • Lymphokines
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • FLT1 protein, human
  • Vascular Endothelial Growth Factor Receptor-1