Marine lipid concentrate and atherosclerosis in the rabbit model

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      Twenty-seven New Zealand white rabbits underwent balloon de-endothelialization of the aorta and iliac arteries while consuming a 2% cholesterol, 10% peanut oil rabbit chow. Ten of these rabbits were fed 1 ml of concentrated marine fish lipid (MaxEpaTm) daily. Six weeks after de-endothelialization, angiography of the treated arteries was performed and histologic cross-sections of the terminal aorta were measured with a planimeter. Iliac artery luminal diameters were also measured at consecutive 3-mm divisions from the aortic bifurcation and found to have a mean lumen diameter of 1.60 ±0.08 mm in the marine lipid-supplemented group (M) and 1.38 ± 0.12 mm in the control group (C) (P < 0.001). Analysis of variance on individual segmental diameters confirmed this difference. However, neither the angiographic diameters nor histologic, cross-sectional, luminal areas of the terminal aorta were different between groups. Instead, the mean cross-sectional area of the terminal aortic wall was significantly greater in the marine lipid-fed group (4.4 ± 1.2 mm2 in M and 3.1 ± 0.6 mm2 in C, P < 0.01). In addition, the vessel wall area showed a positive correlation with red blood cell (RBC) incorporation of docosahexaenoic acid (r = 0.82, P < 0.005) in both groups. In the M group, RBC eicosapentaenoic acid and docosahexaenoic acids increased 100% and 650%, respectively, over baseline. We conclude that marine fish lipids (1) are incorporated into rabbit RBC cell membranes during feeding, (2) increase vessel wall thickness of the distal aorta in proportion to the docosahexaenoic acid present, without compromising the luminal area, and (3) provide mild sparing of the luminal diameters of more distal arteries in this model of atherosclerosis.


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        • Dyerberg J.
        • Bang H.O.
        • Stoffersen E.
        • Moncada S.
        • Vane J.R.
        Eicosapentaenoic acid and prevention of thrombosis and atherosclerosis.
        Lancet. 1978; ii: 117
        • Sinclair J.M.
        Prevention of coronary heart disease: the role of essential fatty acids.
        Postgrad. Med. J. 1980; 56: 579
        • Dyerberg J.
        • Bang H.A.
        Effect on hemostasis by feeding eicosapentaenoic acid.
        in: Nutritional Factors: Modulating Effects on Metabolic Processes. Raven Press, New York1981: 511
        • Stoffersen E.
        • Jorgensen K.A.
        • Dyerberg J.
        Antithrombin III and dietary intake of polyunsaturated fatty acids.
        Scand. J. Clin. Lab. Invest. 1982; 42: 83
        • Kromhout D.
        • Bosschieter E.B.
        • Coulander C.D.
        The inverse relation between fish consumption and 20-year mortality from coronary heart disease.
        New Engl. J. Med. 1985; 312: 1205
        • Yamore Y.
        • Nara Y.
        • Tutani N.
        • Workman R.J.
        • Inagami T.
        Comparison of serum phospholipid fatty acids among fishing and farming Japanese populations and American inlanders.
        J. Nutr. Sci. Vitaminol. 1985; 31: 417
        • Goodnight S.H.
        • Harris W.S.
        • Connor W.E.
        The effects of dietary w3 fatty acids on platelet composition and function in man: a prospective, controlled study.
        Blood. 1981; 58: 880
        • Feramo T.
        • Hirai A.
        • Hamazaki T.
        • Kobayashi S.
        • Fujita T.
        • Tamura Y.
        • Kumagai A.
        Effect of oral administration of highly purified eicosapentaenoic acid on platelet function, blood viscosity and red cell deformability in healthy human subjects.
        Atherosclerosis. 1983; 46: 321
        • Saynor R.
        • Verel D.
        • Gillott T.
        The long-term effect of dietary supplementation with fish lipid concentrate on serum lipids, bleeding time, platelets and angina.
        Atherosclerosis. 1984; 50: 3
        • von Schacky C.
        • Fischer S.
        • Weber P.C.
        Long-term effects of dietary marine ω-3 fatty acids upon plasma and cellular lipids, platelet function, and eicosanoid formation in humans.
        J. Clin. Invest. 1985; 76: 1626
        • von Schacky C.
        • Weber P.C.
        Metabolism and effects on platelet function of the purified eicosapentaenoic and docosahexaenoic acids in humans.
        J. Clin. Invest. 1985; 76: 2446
        • Phillipson B.E.
        • Rothrock D.W.
        • Connor W.E.
        • Harris W.S.
        • Illingworth D.R.
        Reduction of plasma lipids, lipoproteins, and apoproteins by fish oils in patients with hypertriglyceridemia.
        New Engl. J. Med. 1985; 312: 1210
        • Knapp H.R.
        • Reilly I.A.G.
        • Alessandrine P.
        • Fitzgerald G.A.
        In vivo indexes of platelet and vascular function during fish-oil administration in patients with atherosclerosis.
        New Engl. J. Med. 1986; 314: 937
        • Fischer S.
        • Weber P.C.
        Prostaglandin 13 is formed in vivo in man after eicosapentaenoic acid.
        Nature. 1984; 307: 165
        • von Schacky C.
        • Siess W.
        • Fischer S.
        • Weber P.C.
        A comparative study of eicosapentaenoic acid metabolism by human platelets in vivo and in vitro.
        J. Lipid Res. 1985; 26: 457
        • Lea E.J.A.
        • Jones S.P.
        • Hamilton D.V.
        The fatty acids of erythrocytes of myocardial infarction patients.
        Atherosclerosis. 1982; 41: 363
        • Miettinen T.A.
        • Naukkarinen V.
        • Huttunen J.K.
        • Mattila S.
        • Kumlin T.
        Fatty-acid composition of serum lipids predicts myocardial infarction.
        Brit. Med. J. 1982; 285: 993
        • Hay C.R.M.
        • Durber A.P.
        • Gaynor R.
        Effect of fish oil on platelet kinetics in patients with ischemic heart disease.
        Lancet. 1982; i: 1269
        • Friedman R.J.
        • Stemerman M.B.
        • Wenz B.
        • Moore S.
        • Gauldie J.
        • Gent M.
        • Tiell M.L.
        • Spaet T.W.
        The effect of thrombocytopenia on experimental arteriosclerotic lesion formation in rabbits.
        J. Clin. Invest. 1977; 60: 1191
        • Landymore R.E.
        • Kinley C.E.
        • Cooper J.H.
        • MacAulay M.
        • Sheridan B.
        • Cameron C.
        Cod-liver oil in the prevention of intimal hyperplasia in autogeneous vein grafts used for arterial bypass.
        J. Thorac. Cardiovasc. Surg. 1985; 89: 351
        • Weiner B.H.
        • Ockene I.S.
        • Levine P.H.
        • Cuenoud H.F.
        • Fischer M.
        • Johnson B.F.
        • Daoud A.S.
        • Jarmolych J.
        • Hosmer D.
        • Johnson M.H.
        • Natale A.
        • Vaudreuil C.
        • Hoogasian J.J.
        Inhibition of atherosclerosis by cod-liver oil in a hyperlipidemic swine model.
        New Engl. J. Med. 1986; 315: 841
        • Vas Dras F.W.
        • Gibney M.J.
        • Taylor T.G.
        The effect of polyunsaturated fatty acids of the n-3 and n-6 series on platelet aggregation and aortic fatty acid composition in rabbits.
        Atherosclerosis. 1982; 43: 245
        • Thiery J.
        • Seidel D.
        Fish oil feeding results in an enhancement of cholesterol-induced atherosclerosis in rabbits.
        Atherosclerosis. 1987; 63: 53
        • Faxon D.P.
        • Sanborn T.A.
        • Haudenschild C.C.
        • Ryan T.J.
        Effect of antiplatelet therapy on restenosis after experimental angioplasty.
        Am. J. Cardiol. 1984; 53: 72C
        • Scoblionko D.P.
        • Broun B.G.
        • Mitton B.S.
        • Caldwell J.W.
        • Kennedy J.W.
        • Bolson E.L.
        • Dodge H.T.
        A new digital electronic caliper for measurement of coronary arterial stenosis: comparison with visual estimates and computer-assisted measurements.
        Am. J. Cardiol. 1984; 53: 689
        • Meier B.
        • Gruentzig A.R.
        • Goebel N.
        • Pyle R.
        • von Gosslar W.
        • Schlumpf M.
        Assessment of stenosis in coronary angioplasty. Inter- and intraobserver variability.
        Int. J. Cardiol. 1983; 3: 159
        • Allain C.C.
        • Poon L.
        • Chan S.G.
        • Richmond W.
        • Fu P.
        Enzymatic determination of total serum cholesterol.
        Clin. Chem. 1974; 20: 470
        • Lopes-Virella M.F.
        • Stone P.
        • Ellis S.
        • Colwell J.A.
        Cholesterol determination in high density lipoproteins separated by three different methods.
        Clin. Chem. 1977; 23: 882
        • Folch J.
        • Lees M.
        • Sloane-Stanley G.H.
        A simple method for the isolation and purification of total lipids from animal tissues.
        J. Biol. Chem. 1957; 226: 497
        • Snedecor G.W.
        • Cochran W.G.
        Statistical Methods.
        in: State University Press, Ames, IA1980: 290
        • Dixon W.
        BMDP Statistical Software.
        University of California, Berkely, CA1985
        • Faggiotto A.
        • Ross R.
        • Harker L.
        Studies of hypercholesterolemia in the nonhuman primate, I. Changes that lead to fatty steak formation.
        Arteriosclerosis. 1984; 4: 323
        • Faggiotto A.
        • Ross R.
        • Harker L.
        Studies on hypercholesterolemia in the nonhuman primate, II. Fatty streak conversion to fibrous plaque.
        Arteriosclerosis. 1984; 4: 431
        • Ross R.
        • Faggiotto A.
        • Bowen-Pope D.
        • Raines E.
        The role of endothelial injury and platelet and macrophage interactions in atherosclerosis.
        Circulation. 1984; 70: 77
        • Ross R.
        The pathogenesis of atherosclerosis — an update.
        New Engl. J. Med. 1986; 314: 488
        • Ford-Hutchinson A.W.
        Leukotrienes: their formation and role as inflammatory mediators.
        in: 7th edn. Fed. Proc.44. 1985: 25
        • Sirois P.
        Pharmacology of the leukotrienes.
        Adv. Lipid Res. 1985; 21: 79
        • Mathur S.N.
        • Field F.J.
        • Spector A.A.
        • Armstrong M.L.
        Increased production of lipoxygenase products by cholesterol-rich mouse macrophages.
        Biochem. Biophys. Acta. 1985; 837: 13
        • Prescott S.M.
        The effect of eicosapentaenoic acid on leukotriene B production by human neutrophils.
        J. Biol. Chem. 1984; 259: 7615
        • Lee T.
        • Hoover R.L.
        • Williams J.D.
        • Sperling R.I.
        • Ravalese III, J.
        • Spur B.W.
        • Robinson D.R.
        • Corey E.J.
        • Lewis R.A.
        • Austen K.F.
        Effect of dietary enrichment with eicosapentaenoic and docosahexaenoic acids on in vitro neutrophil and monocyte leukotriene generation and neutrophil function.
        New Engl. J. Med. 1985; 312: 1217