title: Overexpression of endothelin-1 and endothelin receptors in the pulmonary arteries of failed Fontan patients.
abstract: BACKGROUND
  Endothelin-1 (ET-1), a potent vasoconstrictor, is considered to be implicated in failing Fontan circulation, however the expressions of ET-1 and endothelin receptor type A (ET(A)R) and type B (ET(B)R) in the pulmonary arteries of failed Fontan patients were not elucidated.
  
  
  METHODS
  Immunohistochemistry and quantitative real-time PCR were used to analyse the expression levels of ET-1 and its receptors in the pulmonary arteries of the autopsy lung tissues of the patients who died after the Fontan procedure (n=10). We divided these patients into 3 groups, failed Fontan (n=4), heart failure (n=3) and non-failed Fontan (n=3), and then compared those to the age-matched normal controls (n=4).
  
  
  RESULTS
  The intra-acinar pulmonary arteries of failed Fontan patients showed significant medial hypertrophy. Computational optical density analyses of the immunostaining revealed that the expressions of ET-1, ET(A)R, and ET(B)R in the intra-acinar pulmonary arteries were significantly increased in the failed Fontan patients (P<0.05 vs. normal controls), however no significant difference was observed between the non-failed Fontan patients and the normal controls. Quantitative real-time PCR analyses confirmed that the mRNA expressions of ET-1, ET(A)R, and ET(B)R were significantly increased in the failed Fontan patients (P<0.05 vs. normal controls).
  
  
  CONCLUSIONS
  The overexpression of ET-1 and its receptors in the pulmonary arteries can cause pulmonary vasoconstriction and vascular remodelling, leading to failed Fontan circulation. This study suggests a histopathological rationale for the potential benefits of endothelin receptor antagonists in patients with failing Fontan circulation.
authors.affiliation: Department of Pediatrics, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Ishida
authors.forename: Shigetoyo
authors.initials: S
authors.lastname: Kogaki
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ichimori
authors.forename: Jun
authors.initials: J
authors.lastname: Narita
authors.forename: Nobutoshi
authors.initials: N
authors.lastname: Nawa
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Ueno
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Takahashi
authors.forename: Futoshi
authors.initials: F
authors.lastname: Kayatani
authors.forename: Hidehumi
authors.initials: H
authors.lastname: Kishimoto
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nakayama
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sawa
authors.forename: Maurice
authors.initials: M
authors.lastname: Beghetti
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ozono
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D019332:Endothelin-1 / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D018729:Fontan Procedure / Q000639:trends; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D011651:Pulmonary Artery / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*; D044022:Receptor, Endothelin A / Q000096:biosynthesis* / Q000235:genetics; D044023:Receptor, Endothelin B / Q000096:biosynthesis* / Q000235:genetics; D017211:Treatment Failure
chemical_list: D019332:Endothelin-1; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B