Omega-3 fatty acids and the regulation of expression of endothelial pro-atherogenic and pro-inflammatory genes.

By partially replacing the corresponding omega-6 analogues in membrane phospholipids, omega-3 fatty acids have been shown to decrease the transcriptional activation of genes--e.g., adhesion molecules, chemoattractants, inflammatory cytokines--involved in endothelial activation in response to inflammatory and pro-atherogenic stimuli. This regulation occurs, at least in part, through a decreased activation of the nuclear factor-kappaB system of transcription factors, secondary to decreased generation of intracellular hydrogen peroxide. Such regulation by omega-3 fatty acids is likely linked to the presence of a higher number of double bonds in the fatty acid chain in omega-3 compared with omega-6 fatty acids. By similar mechanisms, omega-3 fatty acids have been recently shown to reduce gene expression of cyclooxygenase-2, an inflammatory gene involved, through the activation of some metalloproteinases, in plaque angiogenesis and plaque rupture. The quenching of gene expression of pro-inflammatory pro-atherogenic genes by omega-3 fatty acids has consequences on the extent of leukocyte adhesion to vascular endothelium, early atherogenesis and later stages of plaque development and plaque rupture, ultimately yielding a plausible comprehensive explanation for the vasculoprotective effects of these nutrients.