Omega-3 fatty acid supplementation increases plasma resolvin D1 levels, and decreases aortic dissection, in an apoE-/- mouse model of abdominal aortic dissection

Introduction. Resolvin D1 (RVD1), a metabolite of the omega-3 fatty acid docosahexaenoic acid (DHA), is a proresolving mediator. Since abdominal aortic dissection (AAD) has an inflammatory origin (Saraff et al 2003), we hypothesised that prior supplementation of apolipoprotein E-/- angiotensin II-infused (apoE-/- angII) mice with a high DHA-content diet might increase plasma RVD1 concentration, and attenuate the inflammatory response and AAD. Aim. To determine the effect of a low- (L-DHA, negligible content) or high-DHA diet (H-DHA, 0.30%) on plasma RVD1 and neutrophil infiltration, in an apoE-/- and C57 angII AAD mouse model. Methods. Male, 3-4 week apoE-/- and C57 mice received L-DHA or H-DHA for 8 weeks. Mice were infused with angII (1000 ng/kg/min) or 0.9% saline, for 2 days. Plasma RVD1 was determined by enzyme immunoassay, and aorta was embedded, sectioned and stained for neutrophils. Results. Plasma RVD1 concentration was similar in saline-infused C57 L-DHA (374±41 pg/ml, n=10) and H-DHA mice (366±37 pg/ml, n=9). RVD1 concentration was higher in H-DHA, angII-infused C57 mice (584±77 pg/ml, n=10) than the H-DHA, saline-infused C57 mice (P less than 0.05). In apoE-/-, angII-infused mice, RVD1 concentration was higher in H-DHA (743±76 pg/ml, n=9) than L-DHA mice (457±60 pg/ml, n=9; P less than 0.05). Aortic dissection was only observed in angII-infused mice on the L-DHA diet (5/20 mice), with neutrophils localised to the adventitia of these vessels. In angII-infused mice, RVD1 concentration was higher in non-dissected H-DHA (659±56 pg/ml, n=19), than non-dissected L-DHA (469±45 pg/ml, n=15), and dissected L-DHA mice (308±43 pg/ml, n=4; P less than 0.05). Discussion. The pro-inflammatory stimulus plus high DHA diet was associated with elevated plasma RVD1 levels, fewer dissected aortas, and fewer infiltrating neutrophils. The findings suggest that dietary supplementation with HA may increase levels of a pro-resolving mediator, and protect against inflammation in a mouse model of AAD