title: Endothelin receptor expression in human lungs of newborns with congenital diaphragmatic hernia.
abstract: 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.
authors.affiliation: Department of Paediatric Surgery, Hôpital Robert Debré, Paris, France. pascal.delagausie@rdb.ap-hop-paris.fr
authors.forename: Pascal
authors.initials: P
authors.lastname: de Lagausie
authors.forename: Anthony
authors.initials: A
authors.lastname: de Buys-Roessingh
authors.forename: Latifa
authors.initials: L
authors.lastname: Ferkdadji
authors.forename: Julien
authors.initials: J
authors.lastname: Saada
authors.forename: Sophie
authors.initials: S
authors.lastname: Aisenfisz
authors.forename: Christine
authors.initials: C
authors.lastname: Martinez-Vinson
authors.forename: Xavier
authors.initials: X
authors.lastname: Fund
authors.forename: Jean Michel
authors.initials: JM
authors.lastname: Cayuela
authors.forename: Michel
authors.initials: M
authors.lastname: Peuchmaur
authors.forename: Jean Christophe
authors.initials: JC
authors.lastname: Mercier
authors.forename: Dominique
authors.initials: D
authors.lastname: Berrebi
mesh_terms: 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
chemical_list: D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin