Advertisement

Effects of Polyunsaturated Fatty Acids in Endothelium

  • Arthur A. Spector
  • Steven A. Moore

Abstract

The omega-6 polyunsaturated fatty acids are necessary for proper bodily function and health. This class consists of a series of six fatty acids that can be interconverted through elongation, desaturation, and retroconversion.1 The metabolic pathway and the structures of the major components, linoleic acid (18:2) and arachidonic acid (20:4), are illustrated in Fig. 1. Linoleic acid, the main dietary component, can be converted to the other members of the omega-6 series. Prostaglandins and lipoxygenase products are formed from arachidonic acid in animal tissues, including the endothelium. These eicosanoids are especially important for endothelial function. PGI2, the main eicosanoid produced by arterial endothelium, inhibits platelet aggregation and causes relaxation of vascular smooth muscle.2 Several other eicosanoids produced by endothelium, including PGE2,3,4 hydroxy-eicosatetraenoic acids (HETEs),3 and dihydroxyeicosatetraenoic acids (diHETEs),5,6 probably also play a role in endothelial function. Furthermore, linoleic acid can be converted to a hydroxylated metabolite, hydroxyoctadecadienoic acid (HODE),7–9 which can influence the antithrombogenic properties of the endothelial surface as well as modulate eicosanoid formation and degradation.7,9

Keywords

Linoleic Acid Arachidonic Acid Polyunsaturated Fatty Acid Human Umbilical Vein Endothelial Cell Human Endothelial Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Sprecher, H., 1981, Biochemistry of essential fatty acids, Prog. Lipid Res. 20:13–22.PubMedCrossRefGoogle Scholar
  2. 2.
    Moncada, S., 1982, Prostacyclin and arterial wall biology, Arteriosclerosis 2:193–207.PubMedCrossRefGoogle Scholar
  3. 3.
    Mayer, B., Moser, R., Gleispach, H., and Kukovetz, W. R., 1986, Possible inhibitory function of endogenous 15-hydroxyeicosatetraenoic acid on prostacyclin formation in bovine aortic endothelial cells, Biochim. Biophys. Acta 875:641–653.PubMedCrossRefGoogle Scholar
  4. 4.
    Moore, S. A., Spector, A. A., and Hart, M. N., 1988, Eicosanoid metabolism in cerebromicrovascular endothelium, Am. J. Physiol. 254:C37–C44.Google Scholar
  5. 5.
    Hopkins, N. K., Oglesby, T. D., Bundy, G. L., and Gorman, R. R., 1984, Biosynthesis and metabolism of 15-hydroperoxy-5,8,11,13-eicosatetraenoic acid by human umbilical vein endothelial cells, J. Biol. Chem. 259: 14048–14053.PubMedGoogle Scholar
  6. 6.
    Johnson, A. R., Revtyak, G., and Campbell, W. B., 1985, Arachidonic acid metabolites and endothelial injury: Studies with cultures of human endothelial cells, Fed. Proc. 44:19–24.PubMedGoogle Scholar
  7. 7.
    Buchanan, M. R., Haas, T. A., Lagarde, M., and Guichardant, M., 1985, 13-Hydroxyoctadecadienoic acid is the vessel wall chemorepellant factor, LOX, J. Biol. Chem. 260:16056–16059.PubMedGoogle Scholar
  8. 8.
    Takayama, H., Gimbrone, M. A., Jr., and Schaefer, A. I., 1987, Vascular lipoxygenase activity. Synthesis of 15-hydroxyeicosatetraenoic acid from arachidonic acid by blood vessel and cultured vascular endothelial cells, Thromb. Res. 45:803–816.PubMedCrossRefGoogle Scholar
  9. 9.
    Kaduce, T. L., Figard, P. H., Leifur, R., and Spector, A. A., 1989, Formation of 9-hydroxyoctadecadienoic acid from linoleic acid in endothelial cells, J. Biol. Chem. 264:6823–6830.PubMedGoogle Scholar
  10. 10.
    Spector, A. A., Kaduce, T. L., Figard, P. H., Norton, K. C., Hoak, J. C., and Czervionke, R. L., 1983, Eicosapentaenoic acid and prostacyclin production by cultured human endothelial cells, J. Lipid Res. 24: 1595–1604.PubMedGoogle Scholar
  11. 11.
    Hadjiagapiou, C., Kaduce, T. L., and Spector, A. A., 1986, Eicosapentaenoic acid utilization by bovine aortic endothelial cells: Effects on prostacyclin production, Biochim. Biophys. Acta 875:369–381.PubMedCrossRefGoogle Scholar
  12. 12.
    Hadjiagapiou, C., and Spector, A. A., 1987, Docosahexaenoic acid metabolism and effect on prostacyclin production in endothelial cells, Arch. Biochem. Biophys. 253:1–12.PubMedCrossRefGoogle Scholar
  13. 13.
    Yerram, N. R., Moore, S. A., and Spector, A. A., 1989, Eicosapentaenoic acid metabolism in brain microvessel endothelium: Effect on prostaglandin formation, J. Lipid Res. 30:1747–1757.PubMedGoogle Scholar
  14. 14.
    Spector, A. A., Hoak, J. C., Fry, G. L., Denning, G. M., Stoll, L. L., and Smith, J. B., 1980, Effect of fatty acid modification on prostacyclin production by cultured human endothelial cells, J. Clin. Invest. 65:1003–1012.PubMedCrossRefGoogle Scholar
  15. 15.
    Spector, A. A., Kaduce, T. L., Hoak, J. C., and Fry, G. L., 1981, Utilization of arachidonic and linoleic acids by cultured human endothelial cells, J. Clin. Invest. 68:1003–1011.PubMedCrossRefGoogle Scholar
  16. 16.
    Spector, A. A., Kaduce, T. L., Hoak, J. C., and Czervionke, R. L., 1983, Arachidonic acid availability and prostacyclin production by cultured human endothelial cells, Arteriosclerosis 3:323–331.PubMedCrossRefGoogle Scholar
  17. 17.
    Kaduce, T. L., Spector, A. A., and Bar, R. S., 1982, Linoleic acid metabolism and prostaglandin production by cultured bovine pulmonary artery endothelial cells, Arteriosclerosis 2:380–389.PubMedCrossRefGoogle Scholar
  18. 18.
    Denning, G. M., Figard, P. H., Kaduce, T. L., and Spector, A. A., 1983, Role of triglycerides in endothelial arachidonic acid metabolism, J. Lipid Res. 24:993–1001.PubMedGoogle Scholar
  19. 19.
    Figard, P. H., Hejlik, D. P., Kaduce, T. L., Stoll, L. L., and Spector, A. A., 1986, Free fatty acid release from endothelial cells, J. Lipid Res. 27:771–780.PubMedGoogle Scholar
  20. 20.
    Mann, C. J., Kaduce, T. L., Figard, P. H., and Spector, A. A., 1986, Docosatetraenoic acid in endothelial cells: Formation, retroconversion to arachidonic acid, and effect on prostacyclin production, Arch. Biochem. Biophys. 244:813–823.PubMedCrossRefGoogle Scholar
  21. 21.
    Spector, A. A., 1986, Plasma albumin as a lipoprotein, in: Biochemistry and Biology of Plasma Lipoproteins (A. M. Scanu and A. A. Spector, eds.), Dekker, New York, pp. 247–279.Google Scholar
  22. 22.
    Ghinea N., Eskenasy, M., Simionescu, M., and Simionescu, N., 1989, Endothelial albumin binding proteins are membrane-associated components exposed on the cell surface, J. Biol. Chem. 264:4755–4758.PubMedGoogle Scholar
  23. 23.
    Wey, H. E., Jakubowski, J. A., and Deykin, D., 1986, Incorporation and redistribution of arachidonic acid in diacyl and ether phospholipids of bovine aortic endothelial cells, Biochim. Biophys. Acta 878:380–386.PubMedCrossRefGoogle Scholar
  24. 24.
    Hennig, B., Shasby, D. M., Fulton, A. B., and Spector, A. A., 1984, Exposure to free fatty acid increases the transfer of albumin across cultured endothelial monolayers, Arteriosclerosis 4:489–497.PubMedCrossRefGoogle Scholar
  25. 25.
    Stoll, L. L., and Spector, A. A., 1987, Lipid transfer between endothelial and smooth muscle cells in coculture, J. Cell. Physiol. 133:103–110.PubMedCrossRefGoogle Scholar
  26. 26.
    Shasby, D. M., Stoll, L. L., and Spector, A. A., 1987, Polarity of arachidonic acid metabolism by bovine aortic endothelial cell monolayers, Am. J. Physiol. 253:H1177–H1183.Google Scholar
  27. 27.
    Blank, M. L., Spector, A. A., Kaduce, T. L., and Snyder, F., 1986, Composition and incorporation of [3H]arachidonic acid into molecular species of phospholipid classes by cultured human endothelial cells, Biochim. Biophys. Acta 877:211–215.PubMedCrossRefGoogle Scholar
  28. 28.
    Rosenthal, M. D., and Whitehurst, C., 1983, Fatty acyl A6 desaturation activity of cultured human endothelial cells. Modulation by fetal bovine serum, Biochim. Biophys. Acta 750:490–496.PubMedCrossRefGoogle Scholar
  29. 29.
    Rosenthal, M. D., and Hill, J. R., 1984, Human vascular endothelial cells synthesize and release 24- and 26-carbon polyunsaturated fatty acids, Biochim. Biophys. Acta 795:171–178.PubMedCrossRefGoogle Scholar
  30. 30.
    Spector, A. A., Hoak, J. C., Fry, G. L., Stoll, L. L., Tanke, C. T., and Kaduce, T. L., 1981, Essential fatty acid availability and prostacyclin production by cultured human endothelial cells, Prog. Lipid Res. 20:471–477.PubMedCrossRefGoogle Scholar
  31. 31.
    Charo, I. F., Shak, M. A., Karasek, P. M., Davison, P. M., and Goldstein, I. M., 1984, Prostaglandin I2 is not a major metabolite of arachidonic acid in cultured endothelial cells from human foreskin microvessels, J. Clin. Invest. 74:914–919.PubMedCrossRefGoogle Scholar
  32. 32.
    Gerritsen, M. D., and Cheli, C.D., 1983, Arachidonic acid and prostaglandin endoperoxide metabolism in isolated rabbit coronary microvessels and cultivated coronary microvessel endothelial cells, J. Clin. Invest. 72:1658–1671.PubMedCrossRefGoogle Scholar
  33. 33.
    Moore, S. A., Prokuski, L. J., Figard, P. H., Spector, A. A., and Hart, M. N., 1988, Murine cultured microvascular endothelium incorporate and metabolize 12-hydroxyeicosatetraenoic acid, J. Cell. Physiol. 254:C37–C44.Google Scholar
  34. 34.
    Moore, S. A., Figard, P.H., and Spector, A. A., 1989, Brain microvessels produce 12-hydroxyeicosatetraenoic acid, J. Neurochem. 53:376–382.PubMedCrossRefGoogle Scholar
  35. 35.
    Moore, S. A., Yoder, E., and Spector, A. A., 1989, Human microvascular endothelium produce arachidonate (20:4ω-6), eicosapentaenoate (20:5(o-3), and docosahexaenoate (22:6(0–3) from essential fatty acid precursors, FASEB J. 3:A705.Google Scholar
  36. 36.
    Moore, S. A., Yoder, E., and Spector, A. A., 1990, Role of the blood-brain barrier in the formation of long-chain ω-3 and ω-6 fatty acids from essential fatty acid precursors, J. Neurochem. 55:391–402.PubMedCrossRefGoogle Scholar
  37. 37.
    Naughton, J. M., 1981, Supply of polyenoic fatty acids to the mammalian brain: The ease of conversion of the short-chain essential fatty acids to their longer chain polyunsaturates in liver, brain, placenta and blood, Int. J. Biochem. 13:21–32.PubMedCrossRefGoogle Scholar
  38. 38.
    Neuringer, M., Anderson, G. J., and Connor, W. E., 1988, The essentiality of N-3 fatty acids for the development and function of the retina and brain, Annu. Rev. Nutr. 8:517–541.PubMedCrossRefGoogle Scholar
  39. 39.
    Salem, N., Jr., Kim, H.-Y., and Yergey, J. A., 1986, Docosahexaenoic acid: Membrane function and metabolism, in: Health Effects of Polyunsaturated Fatty Acids in Seafoods (A. P. Simopoulos, ed.), Academic Press, New York, pp. 263–317.Google Scholar
  40. 40.
    Holman, R. T., 1986, Nutritional and biochemical evidence of acyl interaction with respect to essential polyunsaturated fatty acids, Prog. Lipid Res. 25:29–39.PubMedCrossRefGoogle Scholar
  41. 41.
    Spector, A. A., Mathur, S. N., Kaduce, T. L., and Hyman, B. T., 1981, Lipid nutrition and metabolism of cultured mammalian cells, Prog. Lipid Res. 19:155–186.CrossRefGoogle Scholar
  42. 42.
    Hyman, B. T., and Spector, A. A., 1981, Accumulation of N-3 polyunsaturated fatty acids by cultured human Y79 retinoblastoma cells, J. Neurochem. 37:60–69.PubMedCrossRefGoogle Scholar
  43. 43.
    Smith, W. L., 1986, Prostaglandin biosynthesis and its compartmentation in vascular smooth muscle and endothelial cells, Annu. Rev. Physiol. 48:251–262.PubMedCrossRefGoogle Scholar
  44. 44.
    Kuhn, H., Ponicke, K., Halle, W., Weisner, R., Schewe, T., and Forster, W., 1985, Metabolism of [l-14C]-arachidonic acid by cultured calf aortic endothelial cells: Evidence for the presence of a lipoxygenase pathway, Prostaglandins Leukotrienes Med. 17:291–303.CrossRefGoogle Scholar
  45. 45.
    Revtyak, G. E., Johnson, A. R., and Campbell, W. B., 1988, Cultured bovine coronary artery endothelial cells synthesize HETEs and prostacyclin, Am. J. Physiol. 254:C8–C19.Google Scholar
  46. 46.
    Campbell, W. B., Falck, J. R., Okita, J. R., Johnson, A. R., and Callahan, K. S., 1985, Synthesis of dihomoprostaglandins from adrenic acid (7,10,13,16-docosatetraenoic acid) by human endothelial cells, Biochim. Biophys. Acta 837:67–76.PubMedCrossRefGoogle Scholar
  47. 47.
    Hong, S. L., and Deykin, D., 1982, Activation of phospholipases A2 and C in pig aortic endothelial cells synthesizing prostacyclin, J. Biol. Chem. 257:7151–7154.PubMedGoogle Scholar
  48. 48.
    Kaya, H., Patton, G. M., and Hong, S. L., 1989, Bradykinin-induced activation of phospholipase A2 is independent of activation of polyphosphoinositide-hydrolyzing phospholipase C., J. Biol. Chem. 264:4972–4977.PubMedGoogle Scholar
  49. 49.
    Spector, A. A., 1988, Lipid and lipoprotein effects on endothelial eicosanoid formation, Semin. Thromb. Hemostasis 14:196–201.CrossRefGoogle Scholar
  50. 50.
    Fleisher, L. N., Tall, A. R., Witte, L. D., Miller, R. W., and Cannon, P. J., 1982, Stimulation of arterial endothelial cell prostacyclin synthesis by high density lipoproteins, J. Biol. Chem. 257:6653–6655.PubMedGoogle Scholar
  51. 51.
    Spector, A. A., Scanu, A. M., Kaduce, T. L., Figard, P. H., Fless, G. M., and Czervionke, R. L., 1985, Effect of human plasma lipoproteins on prostacyclin production by cultured endothelial cells, J. Lipid Res. 26: 288–297.PubMedGoogle Scholar
  52. 52.
    Holland, J. A., Pritchard, K. A., Rogers, N. J., and Stemerman, M. B., 1988, Perturbation of human endothelial cells by atherogenic levels of low density lipoprotein, Am. J. Pathol. 132:474–478.PubMedGoogle Scholar
  53. 53.
    Bordet, J.-C., Guichardant, M., and Lagarde, M., 1988, Hydroperoxides produced by n-6 lipoxygenation of arachidonic and linoleic acids potentiate synthesis of prostacyclin related compounds, Biochim. Biophys. Acta 958:460–468.PubMedCrossRefGoogle Scholar
  54. 54.
    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
  55. 55.
    Knapp, H. R., Reilly, I. A. G., Alessandrini, P., and Fitzgerald, 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
  56. 56.
    Brox, J. H., and Nordoy, A., 1983, The effect of polyunsaturated fatty acids on endothelial cells and their production of prostacyclin, thromboxane and platelet inhibitory activity, Thromb. Hemostasis 50:762–767.Google Scholar
  57. 57.
    Black, K. L., Hoff, J. T., Radin, N. S., and Deshmukh, G. D., 1984, Eicosapentaenoic acid: Effect on brain prostaglandins, cerebral blood flow and edema in ischemic gerbils, Stroke 15:65–69.PubMedCrossRefGoogle Scholar
  58. 58.
    DiCorleto, P. E., and Bowen-Pope, D. F., 1983, Cultured endothelial cells produce a platelet-derived growth factor-like protein, Proc. Natl. Acad. Sci. USA 80:1919–1923.CrossRefGoogle Scholar
  59. 59.
    Fox, P. L., and DiCorleto, P. E., 1988, Fish oils inhibit endothelial cell production of platelet-derived growth factor-like protein, Science 241:453–456.PubMedCrossRefGoogle Scholar
  60. 60.
    Yamaja Setty, B. N., Stuart, M. J., and Walenga, R. W., 1985, Formation of 11-hydroxyeicosatetraenoic acid and 15-hydroxyeicosatetraenoic acid in human umbilical arteries is catalyzed by cyclooxygenäse, Biochim. Biophys. Acta 833:484–494.CrossRefGoogle Scholar
  61. 61.
    Pinto, A., Abraham, N. G., and Mullane, K. M., 1986, Cytochrome P-450-dependentmonoxygenase activity and endothelial-dependent relaxations induced by arachidonic acid, J. Pharmacol. Exp. Ther. 236:445–451.PubMedGoogle Scholar
  62. 62.
    Falck, J. R., Schueler, V. J., Jacobson, H. R., Siddhanta, A. K., Pramanik, B., and Capdevila, J., 1987, Arachidonate epoxygenase: Identification of epoxyeicosatrienoic acids in rabbit kidney, J. Lipid Res. 28: 840–846.PubMedGoogle Scholar
  63. 63.
    Hambrecht, G. S., Adesuyi, S. A., Holt, S., and Ellis, E. F., 1987, Brain 12-HETE formation in different species, brain regions, and in brain microvessels, Neurochem. Res. 12:1029–1033.PubMedCrossRefGoogle Scholar
  64. 64.
    Feinmark, S. J., and Cannon, P. J., 1986, Endothelial cell leukotriene C4 synthesis results from intercellular transfer of leukotriene A4 synthesized by polymorphonuclear leukocytes, J. Biol. Chem. 261:16466–16472.PubMedGoogle Scholar
  65. 65.
    Richards, C. F., Johnson, A. R., and Campbell, W. B., 1986, Specific incorporation of 5-hydroxy-6,8,11,14-eicosatetraenoic acid into phosphatidylcholine in human endothelial cells, Biochim. Biophys. Acta 875: 569–581.PubMedCrossRefGoogle Scholar
  66. 66.
    Schafer, A. I., Takayama, H., Farrell, S., and Gimbrone, M. A., Jr., 1986, Incorporation of platelet and leukocyte lipoxygenase metabolites by cultured vascular cells, Blood 67:373–378.PubMedGoogle Scholar
  67. 67.
    Shen, X.-Y., Figard, P. H., Kaduce, T. L., and Spector, A. A., 1988, Conversion of 15-hydroxyeicosatetra-enoic acid to 11-hydroxyhexadecatrienoic acid by endothelial cells, Biochemistry 27:996–1004.PubMedCrossRefGoogle Scholar
  68. 68.
    Spector, A. A., Gordon, J. A., and Moore, S. A., 1988, Hydroxyeicosatetraenoic acids (HETEs), Prog. Lipid Res. 27:271–323.PubMedCrossRefGoogle Scholar
  69. 69.
    Hadjiagapiou, C., and Spector, A. A., 1986, 12-Hydroxyeicosatetraenoic acid reduces prostacyclin production by endothelial cells, Prostaglandins 31:1135–1144.PubMedGoogle Scholar
  70. 70.
    Honn, K. V., Grossi, I. M., Diglio, C. A., Wojtukiewicz, M., and Taylor, J. D., 1989, Enhanced tumor cell adhesion to the subendothelial matrix resulting from 12(S)-HETE-induced endothelial cell retraction, FASEB J. 3:2285–2293.PubMedGoogle Scholar
  71. 71.
    Gordon, J. A., Figard, P. H., and Spector, A. A., 1990, HETE metabolism in cultured human skin fibroblasts: Evidence for peroxisomal β-oxidation, J. Clin. Invest. 85:1173–1181.PubMedCrossRefGoogle Scholar
  72. 72.
    Nakao, J., Ito, H., Koshihara, Y., and Murota, S., 1984, Age-related increase in the migration of aortic smooth muscle cells induced by 12L-hydroxy-5,8,10,14-eicosatetraenoic acid, Atherosclerosis 51:179–187.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1992

Authors and Affiliations

  • Arthur A. Spector
    • 1
  • Steven A. Moore
    • 2
  1. 1.Department of BiochemistryUniversity of Iowa College of MedicineIowa CityUSA
  2. 2.Department of PathologyUniversity of Iowa College of MedicineIowa CityUSA

Personalised recommendations