The role of linoleic acid in endothelial cell gene expression. Relationship to atherosclerosis.

There is evidence that linoleic acid plays a critical role in gene expression and vascular function as it relates to the pathogenesis of atherosclerosis. The lipid environment, particularly linoleic acid and its derivatives, of the vascular endothelium may profoundly influence the inflammatory response mediated by cytokines. Modulations in the level of activity of a select set of endothelial transcription factors appear to provide a mechanism for linking lipid/cytokine-mediated vessel wall dysfunction, including endothelial cell activation, altered proteoglycan metabolism, and endothelial barrier dysfunction, with the onset of atherosclerotic lesion formation. The activity of endothelial transcription factors is in part regulated by the balance of cellular oxidative stress and antioxidant status. Our data suggest that linoleic acid can activate the vascular endothelium and may thus be an atherogenic fatty acid. Furthermore, nutrients/chemicals with antioxidant properties can protect endothelial cells against lipid-mediated cell injury, suggesting that oxidative stress is a critical component in linoleic acid-mediated gene expression. Our discoveries that linoleic acid can influence significantly the cytokine-mediated inflammatory response may open new fields in dietary intervention of atherosclerosis.