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a Department of
Pediatric Surgery, b Department of Pathology, c Department of Pharmacology, d Sophia
Children's Hospital, Erasmus University, 3015 GJ Rotterdam, The
Netherlands Department of Pediatric Surgery,
Tanta University Hospital, Tanta, Egypt
Correspondence to: Professor Dr D Tibboel.
Received 22 July 1998; Returned to authors 15 October 1998; Revised version received 10 December 1998; Accepted for publication 29 January 1999
BACKGROUND
Pulmonary
hypoplasia accompanied by pulmonary hypertension resistant to treatment
is an important feature of congenital diaphragmatic hernia (CDH). The
pathogenesis of the pulmonary vascular abnormalities in CDH remains to
be elucidated at the molecular level. Vascular endothelial growth
factor (VEGF), an endothelial cell specific mitogen, is known to play a
role in pulmonary angiogenesis and vascular remodelling but there are
no data on VEGF expression in patients with CDH.
METHODSNecroscopic
lung specimens from 21 patients with CDH with lung hypoplasia and from
seven age matched control newborn infants without lung hypoplasia were
processed for immunohistochemical analysis using affinity purified
anti-human VEGF antibodies. All the cases of CDH had pulmonary
hypoplasia, indicated by a lung/body weight index of 
0.012, and
pulmonary hypertension indicated by repeated cardiac ultrasonography.
Cellular localisation of VEGF was semiquantitatively analysed using a
staining score ranging from 0 (no staining) to 4 (very strong staining).
RESULTSSignificantly
raised levels of VEGF immunoreactivity were observed in lung specimens
from cases of CDH compared with controls. VEGF was detected mainly in
the bronchial epithelium and the medial smooth muscle cells of large
(>200 µm) and small (<200 µm) pulmonary arteries, the most
intense staining being in the medial smooth muscle cells of the small
pulmonary arteries. Endothelial cells were positive for VEGF staining
in patients with CDH but not in controls.
CONCLUSIONSThis is
the first study of VEGF expression in newborn infants with CDH.
Increased levels of VEGF, especially in the small, pressure regulating
pulmonary arteries, point to a potential role in vascular remodelling.
This may reflect an unsuccessful attempt by the developing fetus to
increase the pulmonary vascular bed in the hypoplastic lungs to
alleviate the associated pulmonary hypertension.
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