Angiotensin-converting enzyme inhibitor therapy prevents upregulation of endothelin-converting enzyme-1 in failing human myocardium.
In this study, we investigated the role of the renin-angiotensin system in expression of the endothelin system in atrial myocardium of patients with congestive heart failure. Atrial myocardium of control patients without angiotensin-converting enzyme (ACE) inhibitor therapy and heart failure patients without or with ACE inhibitor therapy undergoing aorto-coronary bypass surgery was studied. Endothelin-converting enzyme-1 (ECE-1) expression and endothelin-1 peptide level was upregulated in myocardium of heart failure patients without ACE inhibition. ACE inhibitor therapy prevented upregulation of ECE-1 and endothelin-1 in failing myocardium. Prepro-endothelin-1 and endothelin receptor A expression were not affected by heart failure. Endothelin receptor B was downregulated in heart failure patients. Our data demonstrate an upregulation of ECE-1 mRNA expression in failing human myocardium. Inhibition of the renin-angiotensin system by ACE inhibitor treatment prevents upregulation of ECE-1, suggesting that angiotensin II regulates ECE-1 expression in vivo.
Institute of Pathophysiology, Martin Luther University Halle-Wittenberg, Magdeburger Strasse 18, D-06097 Halle, Germany. henning.morawietz@medizin.uni-halle.de
Henning
H
Morawietz
W
W
Goettsch
M
M
Szibor
M
M
Barton
S
S
Shaw
K
K
Hakim
H-R
HR
Zerkowski
J
J
Holtz
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D015536:Down-Regulation; D000072396:Endothelin-Converting Enzymes; D006321:Heart / Q000187:drug effects*; D006333:Heart Failure / Q000473:pathology*; D006801:Humans; D008666:Metalloendopeptidases; D009206:Myocardium / Q000201:enzymology*; D012333:RNA, Messenger / Q000378:metabolism; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000378:metabolism; D015854:Up-Regulation
D000806:Angiotensin-Converting Enzyme Inhibitors; D012333:RNA, Messenger; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; C000606923:ECE1 protein, human; D000072396:Endothelin-Converting Enzymes