Introduction Dietary omega-3 fatty acids have been associated with protection from atherosclerosis. However, the underlying mechanisms are incompletely understood. Blood flow generate a frictional force on endothelial cells called wall shear stress (WSS) that alters vascular wall function. The aim of this study was to determine whether docosahexaenoic acid (DHA), an omega-3 fatty acid, modulates vascular wall inflammation, blood flow velocity and WSS in experimental atherosclerosis.

Methods ApoE^–/– mice fed either high fat diet (control) or high fat diet plus DHA (300 mg/kg/day) for 12 weeks (n = 12/group). Blood flow velocity was assessed using pulsed wave doppler echocardiography and blood pressure was monitored using Visitech tail-cuff system. Atherosclerosis was measured in whole aorta using enface Oil red O stain, and in aortic roots and brachiocephalic sections stained with Alcian Blue & Elastic Van Gieson stain. Computational flow dynamics (CFD) was used to map WSS magnitude and oscillation in the aorta. Plasma cholesterol levels were quantified by gas chromatography.

Results Plasma high density lipoprotein/total cholesterol ratio was significantly increased in DHA treated mice compared to controls (10.77 ± 1.86 vs. 6.63 ± 1.04, p < 0.05). DHA fed mice exhibited a 4–5 fold reduction in distal aortic and brachiocephalic atherosclerosis (p < 0.01) whereas lesion burden in the aortic arch was similar between groups. Dietary supplementation using DHA led to a reduction in blood pressure (119.5 ± 7.33 mmHg (+DHA) vs. 159.7 ± 2.482 mmHg (controls), p < 0.001 and a 12% decrease in aortic blood flow. CFD revealed that oscillatory shear in the descending aorta was reduced in DHA-fed mice compared to controls.

Conclusions/Implications Our study suggests that dietary DHA can act systemically by enhancing levels of HDL. It can also act locally by reducing oscillatory shear stress in the descending aorta. Dietary DHA reduced lesion formation specifically in the descending aorta, an effect that can be explained by its dual effects on oscillatory shear and HDL. Therefore, the current study suggests novel and interacting protective mechanisms for DHA actions in atherogenesis with implications for the development of dietary interventions to prevent cardiovascular disease.