title: Expression of endothelin-1, endothelin-converting enzyme, and endothelin receptors in chronic heart failure.
abstract: BACKGROUND
  Elevated plasma levels of endothelin (ET)-1 have been reported in association with heart diseases, including heart failure. Furthermore, it has been suggested that ET-1 acts as a local autocrine/paracrine factor with biological activities such as vasoconstriction, mitogenesis, and inotropic effects on the heart. This study investigated alterations of ET-1, ET receptor, and endothelin-converting enzyme (ECE) expression in left ventricular myocardium from patients with end-stage heart failure.
  
  
  RESULTS
  mRNA concentrations of ETA and ETB receptors, prepro-ET-1 (ppET-1), and ECE in left ventricles from nonfailing donors hearts (NF) and from patients with end-stage chronic heart failure (NYHA functional class IV) due to dilated cardiomyopathy (DCM) were compared by use of a competitive reverse transcription-polymerase chain reaction technique. There was no significant difference in mRNA expression for ppET-1, ECE-1, and ETA receptors, whereas a significant reduction of ETB-receptor mRNA was observed in DCM hearts. 125I-labeled ET-1 radioligand binding studies demonstrated a significant downregulation of ETB receptors, whereas ETA-receptor density was increased in membranes from DCM hearts. Phosphoramidon-sensitive ECE activity and immunodetectable amounts of ECE protein in left ventricular membrane preparations did not differ between NF and DCM hearts. Finally, immunoreactive ET-1 concentrations were increased in DCM hearts.
  
  
  CONCLUSIONS
  The present study demonstrates changes in the ET-receptor expression pattern in favor of the ETA receptor in human end-stage heart failure. Furthermore, activation of the cardiac ET system with increased tissue ET-1 concentrations in the failing myocardium is observed. This is more likely due to decreased clearance than to increased synthesis, because ppET-1 gene expression and ECE activity are unchanged.
authors.affiliation: Zentrum für Innere Medizin, Klinik III für Innere Medizin, Universität zu Köln, Cologne, Germany.
authors.forename: O
authors.initials: O
authors.lastname: Zolk
authors.forename: J
authors.initials: J
authors.lastname: Quattek
authors.forename: G
authors.initials: G
authors.lastname: Sitzler
authors.forename: T
authors.initials: T
authors.lastname: Schrader
authors.forename: G
authors.initials: G
authors.lastname: Nickenig
authors.forename: P
authors.initials: P
authors.lastname: Schnabel
authors.forename: K
authors.initials: K
authors.lastname: Shimada
authors.forename: M
authors.initials: M
authors.lastname: Takahashi
authors.forename: M
authors.initials: M
authors.lastname: Böhm
mesh_terms: D016282:Aspartic Acid Endopeptidases / Q000235:genetics*; D009320:Atrial Natriuretic Factor / Q000235:genetics; D017931:DNA Primers; D015536:Down-Regulation; D019332:Endothelin-1 / Q000235:genetics* / Q000378:metabolism; D000072396:Endothelin-Converting Enzymes; D006333:Heart Failure / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D016027:Heart Transplantation; D006801:Humans; D008666:Metalloendopeptidases; D009206:Myocardium / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011869:Radioligand Assay; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D011943:Receptors, Adrenergic, beta / Q000235:genetics / Q000378:metabolism; D017466:Receptors, Endothelin / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
chemical_list: D017931:DNA Primers; D019332:Endothelin-1; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D011943:Receptors, Adrenergic, beta; D017466:Receptors, Endothelin; D009320:Atrial Natriuretic Factor; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; C000606923:ECE1 protein, human; D000072396:Endothelin-Converting Enzymes