Induction of the oxLDL receptor LOX-1 by endothelin-1 in human endothelial cells

Biochem Biophys Res Commun. 2001 Jun 22;284(4):961-5. doi: 10.1006/bbrc.2001.5044.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Transport / drug effects
  • Blotting, Western
  • Cells, Cultured
  • Endothelin Receptor Antagonists
  • Endothelin-1 / pharmacology*
  • Endothelium, Vascular / metabolism*
  • Gene Expression Regulation / drug effects*
  • Humans
  • Kinetics
  • Lipoproteins, LDL / metabolism
  • Oligopeptides / pharmacology
  • Piperidines / pharmacology
  • Protein Kinases / metabolism
  • RNA, Messenger / genetics
  • Receptor, Endothelin B
  • Receptors, LDL / analysis
  • Receptors, LDL / biosynthesis
  • Receptors, LDL / genetics*
  • Receptors, Oxidized LDL
  • Reverse Transcriptase Polymerase Chain Reaction
  • Scavenger Receptors, Class E
  • Transcription, Genetic / drug effects*
  • Umbilical Veins
  • Up-Regulation / drug effects


  • Endothelin Receptor Antagonists
  • Endothelin-1
  • Lipoproteins, LDL
  • OLR1 protein, human
  • Oligopeptides
  • Piperidines
  • RNA, Messenger
  • Receptor, Endothelin B
  • Receptors, LDL
  • Receptors, Oxidized LDL
  • Scavenger Receptors, Class E
  • oxidized low density lipoprotein
  • BQ 788
  • Protein Kinases