Upregulation of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) by 15-lipoxygenase-modified LDL in endothelial cells

Atherosclerosis. 2011 Feb;214(2):331-7. doi: 10.1016/j.atherosclerosis.2010.11.006. Epub 2010 Nov 13.

Abstract

Objective: Lectin-like oxidized LDL receptor-1 (LOX-1), the endothelial receptor for OxLDL, is believed to be responsible for a number of OxLDL-induced effects in the endothelium.

Methods and results: In the present study we showed that LDL modified by 15-lipoxygenase (15LO-LDL), a form of minimally modified lipoprotein, beside its ability to induce pro-inflammatory responses such as oxidative stress and the expression of adhesion molecules, significantly increases LOX-1 expression in endothelial cells, both at transcriptional and at protein level. Such effect is likely to be mediated by p38 MAPK and NF-kB pathways. We then permanently overexpressed LOX-1 in an endothelial cell line and showed that 15LO-LDL were a ligand for LOX-1, and that the interaction LOX-1/15LO-LDL upregulated ICAM-1 surface expression.

Conclusion: Altogether these results indicate minimally modified LDL as a new inducer for LOX-1 expression and as a new ligand for LOX-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arachidonate 15-Lipoxygenase / metabolism*
  • Cells, Cultured
  • Endothelial Cells / metabolism*
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Intercellular Adhesion Molecule-1 / metabolism
  • Ligands
  • Lipoproteins, LDL / metabolism*
  • NF-kappa B / metabolism
  • Oxidative Stress
  • RNA, Messenger / metabolism
  • Rabbits
  • Scavenger Receptors, Class E / genetics
  • Scavenger Receptors, Class E / metabolism*
  • Time Factors
  • Transfection
  • Up-Regulation
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Ligands
  • Lipoproteins, LDL
  • NF-kappa B
  • OLR1 protein, human
  • RNA, Messenger
  • Scavenger Receptors, Class E
  • oxidized low density lipoprotein
  • Intercellular Adhesion Molecule-1
  • Arachidonate 15-Lipoxygenase
  • p38 Mitogen-Activated Protein Kinases