Native and oxidized low-density lipoproteins stimulate endothelin-converting enzyme-1 expression in human endothelial cells.
This study addressed the question how different lipoproteins modulate the expression of endothelin-converting enzyme-1 (ECE-1) in human endothelial cells. The effect of native and oxidized low-density lipoproteins (nLDL, oxLDL) on expression of ECE-1, prepro-endothelin-1, and endothelin-1 peptide was studied in primary cultures of human endothelial cells. Native and oxidized LDL increased ECE-1 mRNA after 1 h, reaching its maximum at 100 microg/ml (1.9- and 2.5-fold, respectively). Furthermore, ECE-1 protein expression, prepro-endothelin-1 mRNA, and endothelin-1 peptide release were increased in response to nLDL or oxLDL. Induction of ECE-1 by nLDL and of prepro-endothelin-1 by oxLDL was reduced by protein kinase C inhibition. Increased expression of ECE-1 mRNA by oxLDL and of prepro-endothelin-1 by nLDL was blocked by an angiotensin II receptor type 1 antagonist. Our data provide evidence for a new mechanism how increased LDL plasma levels might contribute to enhanced endothelin-1 release in patients with hypercholesterolemia.
Niemann
Bernd
B
Department of Vascular Endothelium and Microcirculation, Medical Faculty Carl Gustav Carus, University of Technology Dresden, D-01307 Dresden, Germany.
Rohrbach
Susanne
S
Catar
Rusan A
RA
Muller
Gregor
G
Barton
Matthias
M
Morawietz
Henning
H
D016282:Aspartic Acid Endopeptidases / Q000096:biosynthesis*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology*; D019332:Endothelin-1 / Q000378:metabolism; D000072396:Endothelin-Converting Enzymes; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D019808:Losartan / Q000494:pharmacology; D008666:Metalloendopeptidases / Q000096:biosynthesis*; D010084:Oxidation-Reduction; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism
D019332:Endothelin-1; D007211:Indoles; D008077:Lipoproteins, LDL; D011498:Protein Precursors; D012333:RNA, Messenger; C099252:oxidized low density lipoprotein; D011493:Protein Kinase C; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; C000606923:ECE1 protein, human; D000072396:Endothelin-Converting Enzymes; D019808:Losartan; C064758:Ro 31-8220