Induction of the oxLDL receptor LOX-1 by endothelin-1 in human endothelial cells.
In this study, we analyzed the effect of endothelin-1 (ET-1) on expression of the lectin-like oxidized low-density lipoprotein (oxLDL) receptor-1 LOX-1 and on oxLDL uptake in primary cultures of human umbilical vein endothelial cells (HUVEC). LOX-1 mRNA was quantified by standard-calibrated competitive RT-PCR, LOX-1 protein expression by Western analysis and endothelial oxLDL uptake using DiI-labeled oxLDL. ET-1 induces LOX-1 mRNA expression, reaching its maximum after 1 h (160 +/- 14% of control, 100 nM ET-1, P < 0.05). This increased ET-1-mediated LOX-1 mRNA expression could be inhibited by endothelin receptor B antagonist BQ-788. In addition, ET-1 stimulates LOX-1 protein expression and oxLDL uptake in HUVEC. The augmented oxLDL uptake by ET-1 is mediated by endothelin receptor B, but not by protein kinases. These data support a new pathophysiological mechanism how locally and systemically increased ET-1 levels could promote LOX-1-mediated oxLDL uptake in human endothelial cells and the development and progression of endothelial dysfunction and atherosclerosis.
Morawietz
H
H
Institute of Pathophysiology, Faculty of Medicine, Martin Luther University Halle-Wittenberg, Halle, Germany. henning.morawietz@medizin.uni-halle.de
Duerrschmidt
N
N
Niemann
B
B
Galle
J
J
Sawamura
T
T
Holtz
J
J
D001692:Biological Transport / Q000187:drug effects; D015153:Blotting, Western; D002478:Cells, Cultured; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D044023:Receptor, Endothelin B; D011973:Receptors, LDL / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D051131:Receptors, Oxidized LDL; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051127:Scavenger Receptors, Class E; D014158:Transcription, Genetic / Q000187:drug effects*; D014471:Umbilical Veins; D015854:Up-Regulation / Q000187:drug effects
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D008077:Lipoproteins, LDL; C495137:OLR1 protein, human; D009842:Oligopeptides; D010880:Piperidines; D012333:RNA, Messenger; D044023:Receptor, Endothelin B; D011973:Receptors, LDL; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E; C099252:oxidized low density lipoprotein; C086539:BQ 788; D011494:Protein Kinases