Fatty acids and endothelial cell function: regulation of adhesion molecule and redox enzyme expression.

Different types of dietary fatty acids have distinct, and sometimes opposing, effects on endothelial cell function. Long-chain n-3 polyunsaturated fatty acids from fish oil (eicosapentaenoic-acid-20:5n-3 and docosahexaenoic-acid-22:6n-3) attenuate cytokine-induced adhesion molecule expression (mRNA and protein) while the n-6 polyunsaturated fatty acid arachidonic acid (eicosatetraenoic-acid-20:4n-6) either has no effect, or elicits as up- or down-regulation. Conjugated linoleic acids derived from 18:2n-6, linoleic acid also reduced the expression of adhesion molecules. These polyunsaturated fatty acids also induced redox enzyme expression (mRNA and protein) in endothelial cells and modulation of redox-sensitive transcription factors (e.g. nuclear factor kappa B, activated protein-1) which regulate the gene expression of adhesion molecules, redox enzymes and various stress proteins. The induction of redox enzyme expression by n-3 polyunsaturated fatty acids and conjugated linoleic acids could explain their inhibitory effects on gene transcription and adhesion molecule protein expression. Individual adhesion molecule genes and transcription factors appear to differ in their responsiveness to various oxidant stimuli and non-redox, more direct regulatory mechanisms (e.g. peroxisome proliferator activation receptor activation) might also be involved in their regulation.