Atherogenic ω-6 Lipids Modulate PPAR- EGR-1 Crosstalk in Vascular Cells

Abstract

Atherogenicω-6 lipids are physiological ligands of peroxisome proliferator-activated receptors (PPARs) and elicit pro- and antiatherogenic responses in vascular cells. The objective of this study was to investigate ifω-6 lipids modulated the early growth response-1 (Egr-1)/PPAR crosstalk thereby altering vascular function. Rat aortic smooth muscle cells (RASMCs) were exposed toω-6 lipids, linoleic acid (LA), or its oxidized form, 13-HPODE (OxLA) in the presence or absence of a PPARαantagonist (MK886) or PPARγantagonist (GW9662) or PPAR-specific siRNA. Our results demonstrate thatω-6 lipids, induced Egr-1 and monocyte chemotactic protein-1 (MCP-1) mRNA and protein levels at the acute phase (1–4 hrs) when PPARαwas downregulated and at subacute phase (4–12 hrs) by modulating PPARγ, thus resulting in altered monocyte adhesion to RASMCs. We provide novel insights into the mechanism of action ofω-6 lipids on Egr-1/PPAR interactions in vascular cells and their potential in altering vascular function.