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

Atherogenic ω-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 if ω-6 lipids modulated the early growth response-1 (Egr-1)/PPAR crosstalk thereby altering vascular function. Rat aortic smooth muscle cells (RASMCs) were exposed to ω-6 lipids, linoleic acid (LA), or its oxidized form, 13-HPODE (OxLA) in the presence or absence of a PPARα antagonist (MK886) or PPARγ antagonist (GW9662) or PPAR-specific siRNA. Our results demonstrate that ω-6 lipids, induced Egr-1 and monocyte chemotactic protein-1 (MCP-1) mRNA and protein levels at the acute phase (1-4 hrs) when PPARα was 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 of ω-6 lipids on Egr-1/PPAR interactions in vascular cells and their potential in altering vascular function.