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de Lagausie, P. et al.

de Lagausie, de Buys-Roessingh, Ferkdadji, Saada, Aisenfisz, Martinez-Vinson, Fund, Cayuela, Peuchmaur, Mercier, Berrebi,

Endothelin receptor expression in human lungs of newborns with congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) is a major cause of refractory respiratory failure in the neonatal period and is characterized by persistent pulmonary hypertension of the newborn (PPHN) and pulmonary hypoplasia. Endothelin-1 (ET-1) dysregulation may play a significant role in the pathophysiology of PPHN and ET-1 acts through binding to type A (ETA) and type B (ETB) receptors. Therefore, ETA and ETB receptor protein expression was studied using immunohistochemistry in 10 lung specimens obtained from newborns with CDH, and 4 normal lung specimens, in order to explore whether dysregulation of ETA and ETB expression contributes to PPHN. ETA and ETB mRNAs were then quantified using real-time RT-PCR in laser-microdissected pulmonary resistive arteries. In the lungs of newborns with CDH, immunohistochemistry of both ETA and ETB receptors demonstrated over-expression in the thickened media of pulmonary arteries. Using laser microdissection and real-time RT-PCR, higher levels of ETA and ETB mRNA were found in CDH pulmonary arteries than in controls: this increase was more pronounced for ETA mRNA. This study provides the first demonstration of ET-1 receptor dysregulation in association with structural alteration of pulmonary arteries in newborns with CDH and PPHN. This dysregulation preferentially affects the ETA receptor. These results suggest that dysregulation of ET-1 receptors may contribute to PPHN associated with CDH.[1]

References

Endothelin receptor expression in human lungs of newborns with congenital diaphragmatic hernia. de Lagausie, P., de Buys-Roessingh, A., Ferkdadji, L., Saada, J., Aisenfisz, S., Martinez-Vinson, C., Fund, X., Cayuela, J.M., Peuchmaur, M., Mercier, J.C., Berrebi, D. J. Pathol. (2005) [Pubmed]

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