Omega-3 and omega-6 fatty acids have distinct effects on endothelial fatty acid content and nitric oxide bioavailability
Samuel C.R. Sherratt Prostaglandins, Leukotrienes and Essential Fatty Acids VOLUME 173, 102337, OCTOBER 01, 2021
Highlights
• Endothelial cell (EC) dysfunction is associated with cardiovascular disease and atherosclerosis.
• Eicosapentaenoic acid (EPA) is an omega-3 fatty acid that has been shown to improve nitric oxide (NO) release under disease-like conditions.
• EPA significantly improved NO bioavailability in human ECs compared to DHA and arachidonic acid (AA).
• EPA significantly increased cellular EPA and DPA levels, as well as the EPA/AA ratio.
• DHA and AA treatment significantly increased their respective cellular levels, and did not reproduce EPA-induced DPA or EPA/AA ratio changes.
Treatment with high dose icosapent ethyl (IPE), an ethyl ester of the omega-3 fatty acid eicosapentaenoic acid (EPA), significantly reduced ischemic events in patients with either cardiovascular disease (CV) or diabetes plus other risk factors (REDUCE-IT) but the mechanism is not well understood. We compared the effects of EPA, docosahexaenoic acid (DHA), and the omega-6 fatty acid arachidonic acid (AA) on bioavailability of nitric oxide (NO) and fatty acid composition. Human umbilical vein endothelial cells (HUVECs) were pretreated with EPA, DHA, or AA (10 µM). Cells were stimulated with calcium ionophore and NO and peroxynitrite (ONOO−) were measured using porphyrinic nanosensors. Levels of EPA, DHA, AA and other fatty acids were measured by gas chromatography (GC).
EPA treatment caused the greatest NO release (18%, p < 0.001) and reduction in ONOO− (13%, p < 0.05) compared to control; the [NO]/[ ONOO−] ratio increased by 35% (p < 0.001). DHA treatment increased NO levels by 12% (p < 0.01) but had no effect on ONOO− release. AA did not affect either NO or ONOO− release. Fatty acid treatments increased their respective levels in endothelial cells. EPA levels increased 10-fold to 4.59 mg/g protein (p < 0.001) with EPA treatment and the EPA/AA ratio increased by 10-fold (p < 0.001) compared to vehicle. Only EPA increased docosapentaenoic acid (DPA, omega-3) levels by 2-fold (p < 0.001). AA alone decreased the EPA/AA ratio 4-fold (p<0.001).
These findings support a preferential benefit of EPA on endothelial function and omega-3 fatty acid content.