title: 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.
abstract: 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.
authors.affiliation: Laboratory of Physiology, Faculty of Nutrition, and High Technology Research Center, Kobe Gakuin University, Kobe, Japan. tsutomu@nutr.kobegakuin.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Yamashita
authors.forename: E
authors.initials: E
authors.lastname: Oda
authors.forename: T
authors.initials: T
authors.lastname: Sano
authors.forename: T
authors.initials: T
authors.lastname: Yamashita
authors.forename: Y
authors.initials: Y
authors.lastname: Ijiru
authors.forename: J C
authors.initials: JC
authors.lastname: Giddings
authors.forename: J
authors.initials: J
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000097:blood / Q000178:diet therapy / Q000517:prevention & control*; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D043371:Fatty Acids, Omega-6 / Q000008:administration & dosage*; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics; D013927:Thrombosis / Q000097:blood / Q000178:diet therapy / Q000517:prevention & control*; D014280:Triglycerides / Q000097:blood
chemical_list: D001057:Apolipoproteins E; D004042:Dietary Fats, Unsaturated; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D014280:Triglycerides