PPARgamma agonists enhance human vascular endothelial adhesiveness by increasing ICAM-1 expression

Biochem Biophys Res Commun. 1999 Oct 5;263(3):718-22. doi: 10.1006/bbrc.1999.1437.

Abstract

Early atherosclerotic lesions are characterized by increased monocyte adhesion to the overlying endothelium. Oxidized LDL (oxLDL) stimulates the adhesion of human monocytes to endothelial cells, in part, by increasing expression of ICAM-1. However, the cellular role of oxLDL in endothelial adhesiveness is not well understood. The peroxisome proliferator-activated receptor gamma (PPARgamma), a member of the nuclear receptor superfamily, is expressed in vascular endothelial cells. Whether it can be activated by a synthetic ligand, troglitazone, as well as by natural ligands, oxLDL and its lipid components (i.e., 9- and 13-HODE), has not yet been explored. This study was undertaken to determine whether PPARgamma is expressed in ECV304 human vascular endothelial cells and if so to define the biological effects of its activation by these agonists. Our results demonstrate that PPARgamma mRNA is expressed in ECV304 cells, and transfected cells with a PPARE luciferase construct respond to these agonists. In addition, ligand-dependent PPARgamma activation increased ICAM-1 protein expression and enhanced adherence of monocytes to ECV304 cells by two- to threefold. These findings suggest that the PPARgamma signaling pathway might contribute to the atherogenicity of oxLDL in vascular endothelial cells.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antioxidants / pharmacology
  • Cell Adhesion / drug effects
  • Cell Adhesion / physiology*
  • Cell Line, Transformed
  • Chromans / pharmacology
  • DNA-Binding Proteins / agonists
  • DNA-Binding Proteins / drug effects
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiology*
  • Gene Expression Regulation / drug effects*
  • Humans
  • Intercellular Adhesion Molecule-1 / genetics*
  • Linoleic Acids / pharmacology
  • Linoleic Acids, Conjugated*
  • Lipopolysaccharides / pharmacology
  • Lipoproteins, LDL / pharmacology
  • Receptors, Cytoplasmic and Nuclear / agonists*
  • Receptors, Cytoplasmic and Nuclear / drug effects
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Recombinant Proteins / agonists
  • Recombinant Proteins / drug effects
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thiazoles / pharmacology
  • Thiazolidinediones*
  • Transcription Factors / agonists*
  • Transcription Factors / drug effects
  • Transcription Factors / genetics
  • Transfection
  • Troglitazone
  • Tumor Necrosis Factor-alpha / pharmacology
  • Umbilical Veins

Substances

  • Antioxidants
  • Chromans
  • DNA-Binding Proteins
  • Linoleic Acids
  • Linoleic Acids, Conjugated
  • Lipopolysaccharides
  • Lipoproteins, LDL
  • Receptors, Cytoplasmic and Nuclear
  • Recombinant Proteins
  • Thiazoles
  • Thiazolidinediones
  • Transcription Factors
  • Tumor Necrosis Factor-alpha
  • oxidized low density lipoprotein
  • Intercellular Adhesion Molecule-1
  • 9-hydroxy-10,12-octadecadienoic acid
  • 13-hydroxy-9,11-octadecadienoic acid
  • Troglitazone