Expression of Endothelin-1, Endothelin-Converting Enzyme, and Endothelin Receptors in Chronic Heart Failure
| Autor: | Petra Schnabel, Michael Böhm, Georg Nickenig, Gerhard Sitzler, Jessika Quattek, Oliver Zolk, Thomas Schrader, Masaaki Takahashi, Kohei Shimada |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Inotrope
medicine.medical_specialty Transcription Genetic Endothelin converting enzyme 1 medicine.medical_treatment Down-Regulation Endothelin-Converting Enzymes Radioligand Assay Physiology (medical) Internal medicine Receptors Adrenergic beta medicine Aspartic Acid Endopeptidases Humans RNA Messenger Receptor education DNA Primers Heart Failure Heart transplantation education.field_of_study Endothelin-1 Receptors Endothelin Reverse Transcriptase Polymerase Chain Reaction business.industry Myocardium Metalloendopeptidases Dilated cardiomyopathy Receptor Endothelin A medicine.disease Receptor Endothelin B Endothelin 1 Endocrinology Heart failure Heart Transplantation Cardiology and Cardiovascular Medicine Endothelin receptor business Atrial Natriuretic Factor |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1524-4539 0009-7322 |
| DOI: | 10.1161/01.cir.99.16.2118 |
| Popis: | 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. Methods and Results —mRNA concentrations of ET A and ET B 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 ET A receptors, whereas a significant reduction of ET B -receptor mRNA was observed in DCM hearts. 125 I-labeled ET-1 radioligand binding studies demonstrated a significant downregulation of ET B receptors, whereas ET A -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 ET A 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. |
| Databáze: | OpenAIRE |
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