Ox-LDL plays dual effect in modulating expression of inflammatory molecules through LOX-1 pathway in human umbilical vein endothelial cells

Front Biosci. 2005 Sep 1;10:2585-94. doi: 10.2741/1722.

Abstract

Lectin-like oxidized low-density lipoprotein receptor1 (LOX-1) has been recognized to be the major endothelial receptor for oxidized low-density lipoprotein (ox-LDL). Ox-LDL has been reported to induce the expression of inflammatory adhesive molecules from vascular endothelium. However, the mechanism of this action has not been fully elucidated. Peroxisome proliferation-activated receptor-gamma (PPARgamma) regulates the expression of inflammatory adhesive molecules. The present study was carried out to investigate the role of LOX-1-PPARgamma pathway in regulating expression of adhesion molecules, ICAM-1 and E-selectin in HUVECs. Ox-LDL increased the expression of ICAM-1 and E-selectin in a concentration (10-50 microg/ml)--and time (6-36 hours)--dependent manners. These effects were significantly inhibited by pretreatment of HUVECs with polyinosonic acid or carrageenan. Preincubating HUVECs with 15d-PGJ2 attenuated the expression of ICAM-1 and E-selectin in response to ox-LDL, although ox-LDL stimulated the expression of PPARgamma. Upregulation of ICAM-1 and E-selectin mediated by ox-LDL were inhibited more significantly by the combination of 15d-PGJ2 and polyinosonic acid as compared to either 15d-PGJ2 or polyinosonic acid alone. The results suggested that ox-LDL through its receptor LOX-1 promotes pro-inflammation response by increasing expression of ICAM-1 and E-selectin, simultaneously activates PPARgamma triggering cellular anti-inflammation response in protection from the inflammation lesions in HUVECs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • E-Selectin / metabolism
  • Endothelium, Vascular / metabolism*
  • Humans
  • Intercellular Adhesion Molecule-1 / metabolism
  • Lipoproteins, LDL / metabolism*
  • Scavenger Receptors, Class E / metabolism*
  • Umbilical Veins / cytology*

Substances

  • E-Selectin
  • Lipoproteins, LDL
  • Scavenger Receptors, Class E
  • oxidized low density lipoprotein
  • Intercellular Adhesion Molecule-1