Influence of Polyenoic Acids on Arachidonic Acid Metabolism and Platelet Function

  • Gundu H. R. Rao
  • Nanda P. Kishore
  • Janet D. Peller
  • James G. White
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)


Epidemiologic discoveries suggesting beneficial effects of fish diets in lowering the risk for cardiovascular diseases (CVD) in Greenland Eskimos and Japanese fishermen have prompted many dietary studies aimed at prevention of CVD. Fish fats are rich in -3 polyenoic acids such as eicosa-pentaenoic acid (EPA, 20 : 5) and docosahexaenoic acid (DHA, 22 : 6). Several studies have attributed the salutary influence of a fish diet to the presence of large amounts of these fatty acids. A beneficial effect of polyenoic acids may be related to competitive inhibition of platelet arachidonic acid metabolism or to production of antiplatelet metabolites via the vascular cyclooxygenase or platelet lipoxygenase pathway. In this study we have examined polyenoic-acid-induced in vitro platelet dysfunction and followed the in vivo effects of these fatty acids in modulating ex vivo platelet function. The fatty acids evaluated in this study (EPA and DHA) were potent inhibitors of arachidonic acid conversion to thromboxane. Therefore, they blocked agonist-induced release of granule contents and irreversible aggregation of platelets. However, polyenoic-acid-induced inhibition of thromboxane synthesis was transient and could be reversed by washing platelets. Although radiolabeled polyenoic acids (EPA/DHA) were incorporated into membrane phospholipids, when stirred with agonists they did not generate significant quantities of cyclooxygenase metabolites. Platelets metabolized these fatty acids efficiently via the lipoxygenase pathway. Oral ingestion of two capsules of EPA™ (Shaklee Products, EPA 300 mg; DHA 130 mg) per day for 60 days or 15 capsules per day for 3 days had no significant effect on agonist-induced irreversible aggregation of platelets. Results of our investigation suggest that polyenoic-acid-induced inhibition of platelet function may be related to their ability to compete with substrate arachidonic acid for the active site on the enzyme rather than to the inhibitory metabolites formed via vascular cyclooxygenase or the platelet lipoxygenase pathway. In vivo studies suggest that ingestion of large amounts of the fatty acids may be essential to obtain any beneficial effect.


Fatty Acid Profile Platelet Function Arachidonic Acid Metabolism Platelet Phospholipid Intact Platelet 
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  1. Aharony, D., Smith, J. B., and Silver, M. J., 1982, Regulation of arachidonate-induced platelet aggregation by the lipoxygenase product, 12-hydroperoxyeicosatetraenoic acid, Biochim. Biophys. Acta 718:193–200.Google Scholar
  2. Ahmed, A. A., and Holub, B. J., 1984, Alteration and recovery of bleeding times, platelet aggregation and fatty acid composition of individual phospholipids in platelets of human subjects receiving a supplement of cod liver oil, Lipids 19:617–624.PubMedCrossRefGoogle Scholar
  3. Aveldano, M. J., and Sprecher, H., 1983, Synthesis of hydroxy fatty acids from 4,7,10,13,16,19-[1-14C]docosahexaenoic acid by human platelets, J. Biol. Chem. 258:9339–9343.PubMedGoogle Scholar
  4. Bang, H. O., Dyerberg, J., and Nielsen, B. A., 1971, Plasma lipid and lipoprotein pattern in Greenlandic west-coast Eskimos, Lancet 1:1143–1146.PubMedCrossRefGoogle Scholar
  5. Bild, G. S., Bhat, S. G., and Axelrod, B., 1978, Inhibition of aggregation of human platelets by 8,15-dihydroxyperoxides of 5,9,11,13-eicosapentaenoic acids, Prostaglandins 16:795–801.Google Scholar
  6. Carega, M. M., and Sprecher, H., 1984, Synthesis of two hydroxy fatty acids from 7,10,13,16,19-decosapentaenoic acid by human platelets, J. Biol. Chem. 259:14413–14417.Google Scholar
  7. Dyerberg, J., and Bang, H. O., 1979a, Hemostatic function and platelet polyunsaturated fatty acids in Eskimos, Lancet 2:433–435.PubMedCrossRefGoogle Scholar
  8. Dyerberg, J., Bang, H. O., Stofferson, S., Moncada, S., and Vane, J. R., 1978, Eicosapentaenoic acid and prevention of thrombosis and artherosclerosis, Lancet 2:117–119.PubMedCrossRefGoogle Scholar
  9. Fisher, S., and Weber, P. C., 1983, Thromboxane A3 is formed in human platelets after dietary eicosapentaenoic acid (20 : 53), Biochem. Biophys. Res. Commun. 116:1091–1093.CrossRefGoogle Scholar
  10. Fisher, S., and Weber, P. C., 1984, Prostaglandin I3 is formed in vivo in man after dietary eicosapentaenoic acid, Nature 307:165–168.CrossRefGoogle Scholar
  11. Glomset, J. A., 1985, Fish, fatty acids, and human health, N. Engl. J. Med. 312:1253–1254.PubMedCrossRefGoogle Scholar
  12. Gryglewski, R. J., Salmon, J. A., Ubatuba, F. B., Weatherly, B. C., Moncada, S., and Vane, J. R., 1979, Effects of all-cw-5,8,ll,14,17-eicosapentaenoic acid and PGH3 on platelet aggregation, Prostaglandins 18:453–478.PubMedCrossRefGoogle Scholar
  13. Hirai, A., Hamazaki, T., Terano, T., Nishikawa, T., Tamura, Y., Kumagai, A., and Sajiki, J., 1980, Eicosapentaenoic acid and platelet function in Japanese, Lancet 2:1132–1133.PubMedCrossRefGoogle Scholar
  14. Honstra, G., 1985, Dietary lipids, platelet function and arterial thrombosis, Proc. Nutr. Soc. 44:371–378.CrossRefGoogle Scholar
  15. Knapp, H. R., Reilly, I. A. G., Allessandrini, P., and Fritzgerald, G. A., 1986, In vivo indexes of platelet and vascular function during fish oil administration in patients with atherosclerosis, N. Engl. J. Med. 314:937–942.PubMedCrossRefGoogle Scholar
  16. Kromhout, D., Bosschieter, E. B., and de Lezenne Coulander, C., 1985, The inverse relation between fish consumption and 20 year mortality from coronary heart disease, N. Engl. J. Med. 312:1205–1209.PubMedCrossRefGoogle Scholar
  17. Kuhnlein, H. V., and Innis, S. M., 1986, Distribution of -6 and -3 fatty acids in serum cholesteryl esters of Canadian west coast native Indian men: Relationship to diet and serum cholesterol, Fed. Proc. 45:3973A.Google Scholar
  18. Lokesh, B. R., and Kinsella, J. E., 1985, Lipid composition and prostaglandin synthesis in mouse lung microsomes: Alterations following the ingestion of menhaden oil, Lipids 20:842–849.PubMedCrossRefGoogle Scholar
  19. Needleman, P., Minkes, M. S., and Raz, A., 1976, Thromboxanes: Selective biosynthesis and distinct biological properties, Science 193:163–165.PubMedCrossRefGoogle Scholar
  20. Needleman, P., Raz, A., Minkes, M. S., Ferrendelli, J. A., and Sprecher, S., 1979, Triene prosta glandins: Prostacyclin and thromboxane biosynthesis and unique biological properties, Proc. Natl. Acad. Sci. U.S.A. 76:944–949.PubMedCrossRefGoogle Scholar
  21. Phillipson, B. E., Rothrock, D. W., Connor, W. E., Harris, W. S., and Illingworth, D. R., 1985, Reduction of plasma lipids, lipoproteins, and apoproteins by dietary fish oils in patients with hypertriglyceridemia, N. Engl. J. Med. 312:1210–1216.PubMedCrossRefGoogle Scholar
  22. Rao, G. H. R., and White, J. G., 1985a, Polyenoic acid (PA) metabolism and platelet (PL) function, Thromb. Haemosias. 54:89A.Google Scholar
  23. Rao, G. H. R., and White, J. G., 1985b, Heme-polyenoic acid interaction and prostaglandin synthesis, in: Prostaglandins, Leukotrienes and Lipoxins (J. M. Bailey, ed.), Plenum Press, New York, pp. 357–370.Google Scholar
  24. Rao, G. H. R., and White, J. G., 1985c, Role of arachidonic acid metabolism in human platelet activation and irreversible aggregation, Am. J. Hematol. 19:339–347.PubMedCrossRefGoogle Scholar
  25. Rao, G. H. R., Radha, E., and White, J. G., 1983, Effect of docosahexaenoic acid (DHA) on arachidonic acid metabolism and platelet function, Biochem. Biophys. Res. Commun. 117:549–556.PubMedCrossRefGoogle Scholar
  26. Rao, G. H. R., Radha, E., and White, J. G., 1985, Irreversible platelet aggregation does not depend on lipoxygenase metabolites, Biochem. Biophys. Res. Commun. 131:50–57.PubMedCrossRefGoogle Scholar
  27. Schacky, C., and Weber, P. C., 1985, Metabolism and effects on platelet function of the purified eicosapentaenoic acid docosahexaenoic acids in humans, J. Clin. Invest. 76:2446–2450.CrossRefGoogle Scholar
  28. Vericel, E., and Lagarde, M., 1980, 15-Hydroperoxyeicosatetraenoic acid inhibits human platelet aggregation, Lipids 15:472–474.PubMedCrossRefGoogle Scholar
  29. Whitaker, M. O., Syche, A., Fritzpatrick, F., Sprecher, R. H., and Needleman, P., 1979, Triene prostaglandins: Prostaglandin D3 and eicosapentaenoic acid as potential antithrombotic substances, Proc. Natl. Acad. Sci. U.S.A. 76:5919–5923.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Gundu H. R. Rao
    • 1
  • Nanda P. Kishore
    • 1
  • Janet D. Peller
    • 1
  • James G. White
    • 1
  1. 1.Department of Laboratory Medicine and PathologyUniversity of MinnesotaMinneapolisUSA

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