Regular Article
PPARγ Agonists Enhance Human Vascular Endothelial Adhesiveness by Increasing ICAM-1 Expression

https://doi.org/10.1006/bbrc.1999.1437Get rights and content
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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 γ (PPARγ), 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 PPARγ 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 PPARγ mRNA is expressed in ECV304 cells, and transfected cells with a PPARE luciferase construct respond to these agonists. In addition, ligand-dependent PPARγ activation increased ICAM-1 protein expression and enhanced adherence of monocytes to ECV304 cells by two- to threefold. These findings suggest that the PPARγ signaling pathway might contribute to the atherogenicity of oxLDL in vascular endothelial cells.

Keywords

PPARγ
oxidized LDL
endothelium
intercellular adhesion molecule-1 (ICAM-1)

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1

To whom correspondence should be addressed at Department of Medicine, Stanford University, S-005, 300 Pasteur Dr., Stanford, CA 94305-5103. Fax: 650-725-7085. E-mail: [email protected].