Objective: Very long chain omega-3 fatty acids have been associated with decreased risk of CVD. LDL receptor knockout mice were used to assess the effect of different omega-6:EPA+DHA ratios on atherosclerotic lesion formation and elicited peritoneal macrophage inflammatory response.

Methods and Results: Mice (n=10/group) were fed atherogenic diets for 32 weeks: high fat (20% w/w) without EPA+DHA (HF omega-6), and high fat with omega-6:EPA +DHA ratios of 20:1 (HF R20:1), 4:1 (HF R4:1), and 1:1 (HF R1:1). Aortic total cholesterol was 2.6%, 19.8% and 24.3% lower in the HF R20:1, HF R4:1 and HF R1:1 fed mice, respectively, compared with HF omega-6 fed mice. Elicited peritoneal macrophage cholesteryl ester content (mg/100mg protein) was 4.3 +/-1.3a, 3.9 +/- 1.1ab, 2.6 +/- 0.7b, and 2.7 +/- 0.7b(values with different superscripts are significantly different at P<0.05) in mice fed HF omega-6, HF R20:1, HF R4:1, and HF R1:1 diets, respectively. Peritoneal macrophage membrane fatty acid profile reflected dietary treatment. Elicited peritoneal macrophages isolated from these mice were stimulated with lipopolysaccharide. Monocyte chemoattractant protein-1 (MCP-1) release into the culture medium was 28 +/-7a, 23 +/- 9ab, 18 +/- 8ab, and 17 +/- 6b ng/mg protein in HF omega-6, HF R20:1, HF R4:1, and HF R1:1 diet groups, respectively. Gene expression levels of MCP-1, tumor necrosis factor alpha (TNF-alpha), and ATP-transporter cassette A1 (ABCA1) were significantly lowered in elicited peritoneal macrophages from mice fed HF R1:1 compared to mice fed HF omega-6 diet.

Conclusions: These data suggest that diets with lower omega-6:EPA+DHA ratios resulted in a lower inflammatory response which was associated with less aortic lesion formation.