Increased expression of endothelin-converting enzyme-1 in failing human myocardium.
Endothelin-1 (ET-1) is considered to be involved in the development and progression of heart failure. Therefore, we analysed the expression of endothelin-converting enzyme-1 (ECE-1), endothelin receptors A (ET(A)) and B (ET(B)) mRNAs by standard-calibrated, competitive reverse transcriptase-PCR using an internal-deleted in vitro-transcribed cRNA standard. ET-1 peptide levels were measured using isoform-specific rabbit antibodies against synthetic ET-1. mRNA and protein expression was determined in the right atrial myocardium of New York Heart Association class I patients and class IV patients undergoing aorto-coronary bypass surgery. ECE-1 mRNA was upregulated in failing atrial myocardium. Furthermore, ET-1 peptide levels were increased in failing atrial myocardium. Atrial ET(A) mRNA expression was not changed, while ET(B) mRNA was downregulated in the failing atrial myocardium. Our results support an upregulation of ET-1 synthesis by induction of ECE-1 in failing atrial myocardium. Pharmacological inhibition of augmented ECE-1 expression might provide a new therapeutic perspective in the treatment of heart failure.
Institute of Pathophysiology, Faculty of Medicine, Martin Luther University Halle-Wittenberg, Magdeburger Strasse 18, D-06097 Halle, Germany. henning.morawietz@medizin.uni-halle.de
Henning
H
Morawietz
Winfried
W
Goettsch
Marten
M
Szibor
Matthias
M
Barton
Sidney
S
Shaw
Kavous
K
Hakim
Hans-Reinhard
HR
Zerkowski
Juergen
J
Holtz
D016282:Aspartic Acid Endopeptidases / Q000235:genetics* / Q000378:metabolism; D019332:Endothelin-1 / Q000032:analysis / Q000378:metabolism; D000072396:Endothelin-Converting Enzymes; D004789:Enzyme Activation; D015870:Gene Expression; D006325:Heart Atria; D006333:Heart Failure / Q000201:enzymology*; D006801:Humans; D008666:Metalloendopeptidases; D009206:Myocardium / Q000201:enzymology*; D012333:RNA, Messenger / Q000032:analysis*; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D019332:Endothelin-1; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; C000606923:ECE1 protein, human; D000072396:Endothelin-Converting Enzymes