Document Detail


Pulmonary vascular dysfunction in end-stage cystic fibrosis: role of NF-kappaB and endothelin-1.
MedLine Citation:
PMID:  19460784     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
Pulmonary hypertension is rare in chronic respiratory diseases but has a strong impact on the prognosis and is partly underlined by factors other than hypoxaemia. The aim of the present study was to assess the potential role of endothelin-1 (ET-1) and nuclear factor (NF)-kappaB vasoconstrictive pathways in pulmonary hypertension. The effects of ET-1 receptors blockers (BQ 123 and 788) and of genistein were assessed on response to acetylcholine of pulmonary vascular rings from cystic fibrosis (CF) lung transplant recipients (n = 23). NF-kappaB and ET-1 receptor expression was immunodetected in pulmonary arteries and quantitated using Western blotting. ET-1 vascular content was quantitated using ELISA. In total, 14 out of 23 subjects exhibited strongly impaired pulmonary vasodilation (p<0.01 versus nine out of 23 subjects with a normal response) associated with an activation of ET-1 receptors A and NF-kappaB pathways. Genistein restored vasodilation in subjects with an abnormal response. Pulmonary vascular dysfunction is frequent in end-stage CF, involving the NF-kappaB pathway and that of ET-1 through ET-1 receptor A (ETAR). These data leave a conceptual place for ETAR blockers and isoflavones in the management of the devastating vascular complication of chronic obstructive respiratory diseases such as CF.
Authors:
P Henno; C Maurey; C Danel; P Bonnette; R Souilamas; M Stern; C Delclaux; M Lévy; D Israël-Biet
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-05-21
Journal Detail:
Title:  The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology     Volume:  34     ISSN:  1399-3003     ISO Abbreviation:  Eur. Respir. J.     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-12-01     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8803460     Medline TA:  Eur Respir J     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  1329-37     Citation Subset:  IM    
Affiliation:
UFR Biomédicale des Saints Pères, UPRES EA 4068, Paris, France.
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