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.
De Caterina
R
R
G. d'Annunzio University, Chieti, Italy. rdecater@unich.it
Massaro
M
M
D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D004041:Dietary Fats / Q000378:metabolism*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000378:metabolism*
D016207:Cytokines; D004041:Dietary Fats; D015525:Fatty Acids, Omega-3