Modification of the Arachidonic Acid Cascade by Long-Chain W-3 Fatty Acids

  • Peter C. Weber


Physiological and pathophysiological reactions like vascular resistance, thrombosis, wound healing, inflammation and allergy are modulated by oxygenated metabolites of arachidonic acid (AA; 20:4w−6 or 20:4n−6) and related polyunsaturated fatty acids that are collectively termed eicosanoids. These compounds include prostaglandins, prostacyclin, thromboxane, leukotrienes and other oxygenated derivatives of arachidonic acid. The eicosanoids are all derived from essential fatty acids that must be provided in the diet, and production of eicosanoids is controlled by cellular mechanisms for the uptake, release and oxygenation of the eicosanoid precursor fatty acids.


Platelet Activate Factor Arachidonic Acid Cascade Eicosanoid Formation Thromboxane Formation Eicosanoid Precursor 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Barcelli U, Glas-Greenwalt P, Pollak V.E: Enhancing effect of dietary supplementation with n-3 fatty acids on plasma fibrinolysis in normal subjects. Thromb.Res. 39: 307–312, 1985.PubMedCrossRefGoogle Scholar
  2. 2.
    Cartwright I.J, Pockley A.G, Galloway J.H, Greaves M, Preston F.E: The effects of dietary n-3 polyunsaturated fatty acids on erythrocyte membrane phospholipids, erythrocyte deformability and blood viscosity in healthy volunteers. Atherosclerosis 55: 267–281, 1985.PubMedCrossRefGoogle Scholar
  3. 3.
    Dyerberg J, Bang H.O, Stofferson E, Moncada S, Vane J.R: Eicosapentaenoic acid and prevention of thrombosis and atherosclerosis? Lancet 1: 117–119, 1978.CrossRefGoogle Scholar
  4. 4.
    Fischer S, v.Schacky C, Siess W, Strasser T, Weber P.C: Uptake, release and metabolism of docosahexaenoic acid (DCHA, C22:6n-3) in human platelets and neutrophils. Biochem.Biophys.Res.Commun. 120: 907–819, 1984.PubMedCrossRefGoogle Scholar
  5. 5.
    Fischer S, Weber, P.C: Thromboxane A3 (TXA3) is formed in human platelets after dietary eicosapentaenoic acid (C20:5n-3). Biochem.Biophys.Res.Commun. 116: 1091–99, 1983.PubMedCrossRefGoogle Scholar
  6. 6.
    Fischer S, Weber P.C: Prostaglandin I3 is formed in vivo in man after dietary eicosapentaenoic acid. Nature (Lond.) 307: 165–168, 1984.CrossRefGoogle Scholar
  7. 7.
    Fischer S, Vischer A, Preac-Mursic V, Weber P.C: Dietary docosahexaenoic acid is retroconverted in man to eicosapentaenoic acid, which can be quickly transformed to prostaglandin I3. Prostaglandins 34: 367–375, 1987.PubMedCrossRefGoogle Scholar
  8. 8.
    Galloway J.H, Cartwright I.J, Woodcock B.E, Greaves M, Russel R.G.G, Preston F.E: Effects of dietary fish oil supplementation on the fatty acid composition of the human platelet membrane: demonstration of selectivity in the incorporation of eicosapentaenoic acid into membrane phospholipid pools. Clin.Sci. 68: 449–454, 1985.PubMedGoogle Scholar
  9. 9.
    Goto Y: Serum cholesterol and nutrition in Japan. Nutrition and Health 3: 255–257, 1985.PubMedGoogle Scholar
  10. 10.
    Illingworth D.R, Harris W.S, Connor W.E: Inhibition of low density lipoprotein synthesis by dietary omega-3 fatty acids in humans. Arteriosclerosis 4: 270–275, 1984.PubMedCrossRefGoogle Scholar
  11. 12.
    Kromann N, Green A: Epidemiological studies in the Upernavik district, Greenland. Acta Med.Scand. 208: 401–406, 1980.PubMedCrossRefGoogle Scholar
  12. 13.
    Lee T H, Hoover R.L, Willians J.D, Sperling, R.I, Revalese 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. N.Engl.J.Med. 312: 1217–1224, 1985.PubMedCrossRefGoogle Scholar
  13. 14.
    Lorenz R, Spengler U, Fischer S, Duhm J, Weber P.C: Platelet function, thromboxane formation and blood pressure control during supplementation of the western diet with cod liver oil. Circulation 67: 504–511, 1983.PubMedCrossRefGoogle Scholar
  14. 15.
    Nagakava Y, Orimo H, Harasawa M, Morita I, Yashiro K, Murota S: Effect of eicosapentaenoic acid on the platelet aggregation and composition of fatty acids in man. Atherosclerosis 47: 71–75, 1983.CrossRefGoogle Scholar
  15. 16.
    Nestel P.J, Connor W.E, Reardon M.R, Connor S., Wong S, Boston R: Suppression by diets rich in fish oil of very low density lipoprotein production in man. J.Clin.Invest. 74: 82–89, 1984.PubMedCrossRefGoogle Scholar
  16. 17.
    Phillipson B.E:, Rothrock, D.W, Connor W.E, Harris N.S, Illingworth R: Reduction of plasma lipids, lipoproteins and apoproteins by dietary fish oils in patients with hypertriglyceridemia. N.Engl.J. Med. 312: 1210–16, 1985.Google Scholar
  17. 18.
    Prickett J.D, Robinson D.R and Steinberg A.D: Dietary enrichment with the polyunsaturated fatty acid eicosapentaenoic acid prevents proteinuria and prolongs survival in NZBxNZW F1 mice. J.Clin.Invest. 68: 556–559, 1981.PubMedCrossRefGoogle Scholar
  18. 19.
    Robinson R, Snyder F: Metabolism of platelet activating factor by rat alveolar macrophages: lyso-PAF as an obligatory intermediate in the formation of alkyl-arachidonoyl-glycerophosphocholine species. Biochem.Biophys.Acta 837: 52–56, 1985.PubMedCrossRefGoogle Scholar
  19. 20.
    v.Schacky C, Fischer S, Weber P.C: Long term effects of dietary marine n-3 fatty acids upon plasma and cellular lipids, platelet function and eicosanoid formation in humans. J.Clin.Invest. 76: 1626–31, 1985.CrossRefGoogle Scholar
  20. 21.
    v.Schacky C, Weber P.C: Metabolism and effects on platelet function of the purified eicosapentaenoic and docosahenaenoic acids in humans. J.Clin.Invest. 76: 2446–50, 1985.CrossRefGoogle Scholar
  21. 22.
    v.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. 26: 457–464, 1985.Google Scholar
  22. 23.
    Siess W, Roth P, Scherer B, Kurzmann I, Boehlig B, Weber P.C: Platelet membrane fatty acids, platelet aggregation and thromboxane formation during a mackerel diet. Lancet 1: 441–444, 1980.PubMedCrossRefGoogle Scholar
  23. 24.
    Singer P, Wirth M, Voigt S, Richter-Heinrich E, Gödicke W, Berger I, Naumann E, Listing J, Hathrodt M, Taube, Ch: Blood pressure and lipid-lowering effect of mackerel and herring diet in patients with mild essential hypertension. Atherosclerosis 56: 223–235, 1985.PubMedCrossRefGoogle Scholar
  24. 25.
    Singer P, Berger I, Wirth M, Gödicke W, Jaeger W, Vogt S: Slow desaturation•and elongation of linoleic and a-linolenic acids as a rationale of eicosapentaenoic acid-rich diet to lower blood pressure and serum lipids in normal, hypertensive and hyperlipidemic subjects. Prostagl.Leukotr.Med. 24: 173–193, 1986.CrossRefGoogle Scholar
  25. 26.
    Strasser T, Fischer S, Weber P.C: Leukotriene B5 is formed in human neutrophils after dietary eicosapentaenoic acid. Proc.Natl.Acad.Sci, USA 82: 1540 1543, 1985.Google Scholar
  26. 27.
    Sugiura T, Masuzawa Y, Waku K: Transacylation of 1–0-alkyl-sn-glycero-3-phosphocholine (lyso platelet activating factor) and l-0-alkenyl-sn-glycero-3-phosphoethanolamine with docosahexaenoic acid (C22–6w-3). Biochem.Biophys.Res.Commun. 133: 574–580, 1985.PubMedCrossRefGoogle Scholar
  27. 28.
    Tinoco J: Dietary requirement and functions of alinolenic acid in animals. Prog.Lipid.Res. 21: 145, 1982.CrossRefGoogle Scholar
  28. 29.
    Yamori Y, Nara Y, Iritani N, Workman R.J, Inagami T; Comparison of serum phospholipid fatty acids among fishing and farming Japanese populations and American inlanders. J.Nutr.Vitaminol.(Tokyo), 31: 417–22, 1985.CrossRefGoogle Scholar
  29. 30.
    Weber P.C, Fischer S, v.Schacky C, Lorenz R, Strasser T: The conversion of dietary eicosapentaenoic acid to prostanoids and leukotrienes in man. Progr.Lipid. Res. 25; 273–276, 1986.Google Scholar
  30. 31.
    Weber P.C: The dietary modification of the arachidonic acid cascade. In: Biology of eicosanoids and related substances in blood and vascular cells. Colloque INSERM 152: 119–126, 1987.Google Scholar
  31. 32.
    Leaf A, Weber P.C: Cardiovascular effects of n-3 fatty acids. N.Engl.J.Med. 318: 549–557, 1988.PubMedCrossRefGoogle Scholar
  32. 33.
    Endres S, Kelley V.E, Dinarello C.A: Effects of dietary omega-3 fatty acids on the in vitro production of human interleukin I. J.Leukoc.Biol. 42: 617, 1987.Google Scholar
  33. 34.
    Fox P, Di Corleto E: Fish oils inhibit endothelial cell production of platelet-derived growth factor-like protein. Science 241: 453–456, 1988.PubMedCrossRefGoogle Scholar
  34. 35.
    Hstmark A, Bierkedal T, Kierulf P, Flaten H, Ulshagen K: Fish oil and plasma fibrinogen. Br.Med.J. 297: 180–181, 1988.CrossRefGoogle Scholar
  35. 36.
    Dehmer G.J, Jeffrey J, Popma J, v.d.Berg E.K, Eichhorn E.J, Prewitt J.B, Campbell W.B, Jennings L, Willerson J.T, Schmitz J.M: Reduction in the rate of early restenosis after coronary angioplasty by a diet supplemented with n-3 fatty acids. N.Engl.J. Med. 319: 733–740, 1988Google Scholar

Copyright information

© Springer Science+Business Media New York 1989

Authors and Affiliations

  • Peter C. Weber
    • 1
  1. 1.Institut fur die Prophylaxe der Kreislaufkrankheitenb.d. Universitat MunchenMunchen 2Germany

Personalised recommendations