title: Influence of Mechanical Circulatory Support on Endothelin Receptor Expression in Human Left Ventricular Myocardium from Patients with Dilated Cardiomyopathy (DCM).
abstract: BACKGROUND
  In terminal failing hearts ventricular assist devices (VAD) are implanted as a bridge to transplantation. Endothelin receptor (ETR) antagonists are used for treatment of secondary pulmonary hypertension in VAD patients. However, the cardiac ETR regulation in human heart failure and during VAD support is incompletely understood.
  
  
  METHODS
  In paired left ventricular samples of 12 dilated cardiomyopathy patients we investigated the density of endothelin A (ETA) and B (ETB) receptors before VAD implantation and after device removal. Left ventricular samples of 12 non-failing donor hearts served as control. Receptor quantification was performed by binding of [125I]-ET-1 in the presence of nonselective and ETA selective ETR ligands as competitors. Additionally, the ETR mRNA expression was analyzed using quantitative real-time-PCR.
  
  
  RESULTS
  The mRNA of ETA but not ETB receptors was significantly elevated in heart failure, whereas total ETR density analyzed by radioligand binding was significantly reduced due to ETB receptor down regulation. ETA and ETB receptor density showed poor correlation to mRNA data (spearman correlation factor: 0.43 and 0.31, respectively). VAD support had no significant impact on the density of both receptors and on mRNA expression of ETA whereas ETB mRNA increased during VAD. A meta-analysis reveals that the ETA receptor regulation in human heart failure appears to depend on non-failing hearts.
  
  
  CONCLUSIONS
  In deteriorating hearts of patients suffering from dilated cardiomyopathy the ETA receptor density is not changed whereas the ETB receptor is down regulated. The mRNA and the proteins of ETA and ETB show a weak correlation. Non-failing hearts might influence the interpretation of ETA receptor regulation. Mechanical unloading of the failing hearts has no impact on the myocardial ETR density.
authors.affiliation: Erich & Hanna Klessmann Institute for Cardiovascular Research and Development, Clinic for Thoracic and Cardiovascular Surgery, Heart and Diabetescenter NRW, Bad Oeynhausen, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Gärtner
authors.affiliation: Institute of Pharmacology, Pharmacy and Toxicology, University of Leipzig, Leipzig, Germany.
authors.forename: Getu
authors.initials: G
authors.lastname: Abraham
authors.affiliation: Erich & Hanna Klessmann Institute for Cardiovascular Research and Development, Clinic for Thoracic and Cardiovascular Surgery, Heart and Diabetescenter NRW, Bad Oeynhausen, Germany.
authors.forename: Astrid
authors.initials: A
authors.lastname: Kassner
authors.affiliation: Erich & Hanna Klessmann Institute for Cardiovascular Research and Development, Clinic for Thoracic and Cardiovascular Surgery, Heart and Diabetescenter NRW, Bad Oeynhausen, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Baurichter
authors.affiliation: Erich & Hanna Klessmann Institute for Cardiovascular Research and Development, Clinic for Thoracic and Cardiovascular Surgery, Heart and Diabetescenter NRW, Bad Oeynhausen, Germany.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Milting
mesh_terms: D015153:Blotting, Western; D002311:Cardiomyopathy, Dilated / Q000378:metabolism* / Q000601:surgery*; D016022:Case-Control Studies; D006352:Heart Ventricles / Q000378:metabolism*; D006353:Heart-Assist Devices; D006801:Humans; D007124:Immunoenzyme Techniques; D009206:Myocardium / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D044022:Receptor, Endothelin A / Q000235:genetics / Q000378:metabolism*; D044023:Receptor, Endothelin B / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016277:Ventricular Function, Left / Q000502:physiology
chemical_list: D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B