PPARgamma agonists enhance human vascular endothelial adhesiveness by increasing ICAM-1 expression.
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.
Chen
N G
NG
Department of Medicine, Stanford University School of Medicine, Stanford, California 94305, USA. jchen@gcrc.stanford.edu
Sarabia
S F
SF
Malloy
P J
PJ
Zhao
X Y
XY
Feldman
D
D
Reaven
G M
GM
D000975:Antioxidants / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D002461:Cell Line, Transformed; D002839:Chromans / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000819:agonists / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D008041:Linoleic Acids / Q000494:pharmacology; D044243:Linoleic Acids, Conjugated; D008070:Lipopolysaccharides / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000187:drug effects / Q000235:genetics; D011994:Recombinant Proteins / Q000819:agonists / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000819:agonists* / Q000187:drug effects / Q000235:genetics; D014162:Transfection; D000077288:Troglitazone; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins
D000975:Antioxidants; D002839:Chromans; D004268:DNA-Binding Proteins; D008041:Linoleic Acids; D044243:Linoleic Acids, Conjugated; D008070:Lipopolysaccharides; D008077:Lipoproteins, LDL; D018160:Receptors, Cytoplasmic and Nuclear; D011994:Recombinant Proteins; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; C099252:oxidized low density lipoprotein; D018799:Intercellular Adhesion Molecule-1; C024347:9-hydroxy-10,12-octadecadienoic acid; C024348:13-hydroxy-9,11-octadecadienoic acid; D000077288:Troglitazone