Thorax 1999;54:427-431 ( May )

Enhanced expression of vascular endothelial growth factor in lungs of newborn infants with congenital diaphragmatic hernia and pulmonary hypertension

Sherif M K Shehata,^{a d} Wolter J Mooi,^b Tadaharu Okazaki,^{a c} Ibrahim El-Banna,^d Hari S Sharma,^c Dick Tibboel^a

^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

BACKGROUNDPulmonary 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.


Keywords: congenital diaphragmatic hernia; pulmonary hypertension; vascular endothelial growth factor; angiogenesis; immunohistochemistry

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© 1999 by Thorax
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