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.
de Lagausie
Pascal
P
Department of Paediatric Surgery, Hôpital Robert Debré, Paris, France. pascal.delagausie@rdb.ap-hop-paris.fr
de Buys-Roessingh
Anthony
A
Ferkdadji
Latifa
L
Saada
Julien
J
Aisenfisz
Sophie
S
Martinez-Vinson
Christine
C
Fund
Xavier
X
Cayuela
Jean Michel
JM
Peuchmaur
Michel
M
Mercier
Jean Christophe
JC
Berrebi
Dominique
D
D001835:Body Weight; D005260:Female; D015870:Gene Expression; D006548:Hernia, Diaphragmatic / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D065630:Hernias, Diaphragmatic, Congenital; D006801:Humans; D007231:Infant, Newborn; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D042282:Microdissection / Q000379:methods; D009929:Organ Size; D010547:Persistent Fetal Circulation Syndrome / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D011651:Pulmonary Artery / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D044022:Receptor, Endothelin A / Q000235:genetics / Q000378:metabolism; D044023:Receptor, Endothelin B / Q000235:genetics / Q000378:metabolism; D017466:Receptors, Endothelin / Q000378:metabolism*; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin