Varying the ratio of dietary n−6/n−3 polyunsaturated fatty acid alters the tendency to thrombosis and progress of atherosclerosis in apoE−/− LDLR−/− double knockout mouse

We have investigated the influence of dietary n−6/n−3 (ù-6/ù-3) polyunsaturated fatty acid-balance on the tendency to arterial thrombosis and the progress of atherosclerosis in apoE−/− LDLR−/− double knockout mouse. Homozygous apoE−/− LDLR−/− double knockout mouse (DKO mice, 129XC57BL/6J background) and male C57BL/6 mice aged 6 weeks were divided into four groups. Each group was fed a diet containing a different n−6/n−3 ratio (Group l: 0.29; Group 2: 1.43; Group 3: 5.00; Group 4: 8), prepared with high linolenic (LNA) flaxseed oil (n−3 rich) and high linoleic (LA) safflower oil (n−6 rich). There were no statistical differences in the gain in body weight between the four groups. After 16 weeks, plasma triglyceride and LDL levels in Group 1 were significantly lower than in the other groups. Conversely, HDL was the highest. After 8 and 16 weeks, the tendency to arterial thrombosis was assessed using a He-Ne laser-induced thrombosis model. The degree of atherosclerosis was measured using the entire aorta method employing image analysis software. The n−6/n−3 ratio had a dose-dependent antithrombotic effect (thrombus volume decreased 23%, Group 1 vs. Group 4), In addition, the extent of atherosclerosis was less in the animals fed a low n−6/n−3 ratio compared with the high n−6/n−3 ratio group (atherosclerotic area decreased 40%, Group 1 vs. Group 4). The lowest n−6/n−3 ratio tested (0.29) was the most effective in suppressing the thrombotic and atherosclerotic parameters in these DKO mice.