The anti-atherogenic effects of eicosapentaenoic and docosahexaenoic acid are dependent on the stage of THP-1 macrophage differentiation

• LC n-3 PUFA specific effects on initial stages of atherosclerosis.
• Investigation of effects on an early and late stage macrophage differentiation model.
• Differentiation markers and scavenger receptors are more affected in early stages.
• DHA can affect lipoprotein receptor levels in late stage differentiation.
• LC n3/n6 PUFA decrease basal cholesterol levels in early stage macrophages.

In this study LC n-3 PUFA-specific effects on the degree of monocyte differentiation and macrophage foam cell formation were investigated by treating PMA-induced immature and mature macrophage models with LC n-3/n-6 PUFA during and post-differentiation. During immature macrophage differentiation LC n-3 PUFA alone decreased TNFα mRNA levels. EPA, and the n-6 PUFAs, linoleic acid and arachidonic acid, decreased CD36 mRNA levels, and EPA also downregulated CD49d cell-surface expression. Both LC n-3 PUFA reduced LDLr mRNA levels in immature macrophages, while DHA alone reduced levels in mature macrophages. Post-differentiation, n-3 and -6 PUFA reduced basal, but not oxidised LDL dependent cholesterol levels in immature macrophages. LC n-3 PUFA-specific reductions in LDLr and LOX-1 mRNA expression were also observed.This study found LC n-3 PUFA specific, anti-atherogenic effects were more significant in immature macrophages. LC n-3 PUFA effects may be modulated by the extent of monocyte to macrophage differentiation.