Document Detail


Overexpression of endothelin-1 and endothelin receptors in the pulmonary arteries of failed Fontan patients.
MedLine Citation:
PMID:  21356562     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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). CONCLUSION: 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:
Hidekazu Ishida; Shigetoyo Kogaki; Hiroaki Ichimori; Jun Narita; Nobutoshi Nawa; Takayoshi Ueno; Kunihiko Takahashi; Futoshi Kayatani; Hidehumi Kishimoto; Masahiro Nakayama; Yoshiki Sawa; Maurice Beghetti; Keiichi Ozono
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-2-26
Journal Detail:
Title:  International journal of cardiology     Volume:  -     ISSN:  1874-1754     ISO Abbreviation:  -     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-3-1     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8200291     Medline TA:  Int J Cardiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Affiliation:
Department of Pediatrics, Osaka University Graduate School of Medicine, Osaka, Japan.
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