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

Thromb Res. 2005;116(5):393-401. doi: 10.1016/j.thromres.2005.01.011. Epub 2005 Feb 25.


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.

MeSH terms

  • Animals
  • Apolipoproteins E / deficiency
  • Apolipoproteins E / genetics
  • Atherosclerosis / blood
  • Atherosclerosis / diet therapy
  • Atherosclerosis / prevention & control*
  • Dietary Fats, Unsaturated / administration & dosage
  • Fatty Acids, Omega-3 / administration & dosage*
  • Fatty Acids, Omega-6 / administration & dosage*
  • Lipoproteins, HDL / blood
  • Lipoproteins, LDL / blood
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, LDL / deficiency
  • Receptors, LDL / genetics
  • Thrombosis / blood
  • Thrombosis / diet therapy
  • Thrombosis / prevention & control*
  • Triglycerides / blood


  • Apolipoproteins E
  • Dietary Fats, Unsaturated
  • Fatty Acids, Omega-3
  • Fatty Acids, Omega-6
  • Lipoproteins, HDL
  • Lipoproteins, LDL
  • Receptors, LDL
  • Triglycerides