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Albumin-bound docosahexaenoic acid and collagen-induced human platelet reactivity

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Lipids

Abstract

Anin vitro system designed to mimic the effect of various plasma nonesterified (polyunsaturated) fatty acids on platelet function and metabolism was employed. Human platelet aggregation induced by submaximal (1.8 μg/ml) collagen stimulation was significantly inhibited by 2 min preincubation with 20 μM albumin-bound docosahexaenoic acid (22∶6n−3) (DHA), but not by the other fatty acids tested. [3H]Phosphatidic acid (PA) formation, an indicator of phospholipase C activation following platelet stimulation, was moderately inhibited by eicosapentaenoic acid (20∶5n−3), 11,14,17-eicosatrienoic acid (20∶3n−3), dihomo-γ-linolenic acid (20∶3n−6), as well as DHA, but not by arachidonic acid (20∶4n−6); this inhibition of phospholipase C activation could not explain the differential effect of DHA on platelet aggregation. The decreased production of thromboxane A2 (TxA2), as assessed by [3H]12-hydroxy-5,8,10-heptadecatrienoic acid (HHT) formation, may account for the inhibition of collagen-induced aggregation by 20 μM DHA. Surprisingly, preincubation with 40 μM albumin-bound DHA, even though resulting in greater inhibition of collagen-induced aggregation, had less impact on HHT formation. A small but significant increase in [3H]prostaglandin D2 (PGD2) levels following 3-min collagen stimulation may have contributed to the greater antiaggregatory effect of 40 μM DHA. It is concluded that increased plasma nonesterified DHA may contribute to the dampened platelet activation and altered metabolism following fish oil supplementation of the diet.

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Abbreviations

AA:

arachidonic acid

DG:

diacylglycerol

DHA:

docosahexaenoic acid

EPA:

eicosapentaenoic acid

FFA:

free fatty acids

HETE:

hydroxyeicosatetraenoic acid

HHT:

hydroxy-heptadecatrienoic acid

TP3 :

inositol trisphosphate

NEFA:

nonesterified fatty acid

PA:

phosphatidic acid

PGD2 :

prostaglandin D2

TxA2 :

thromboxane A2

TxB2 :

thromboxane B2

References

  1. Dyerberg, J., and Bang, H.O. (1979)Lancet 2, 433–435.

    Article  PubMed  CAS  Google Scholar 

  2. Hirai, A., Hamakazi, T., Terano, T., Nishikawa, T., Tamura, Y., and Kumagai, A. (1980)Lancet 2, 1132–1133.

    Article  PubMed  CAS  Google Scholar 

  3. Kromhout, D., Bosschieter, E.B., and Coulander, L.L. (1985)N. Engl. J. Med. 312, 1205–1209.

    Article  PubMed  CAS  Google Scholar 

  4. Herold, P.M., and Kinsella, J.E. (1986)Am. J. Clin. Nutr. 43, 566–598.

    PubMed  CAS  Google Scholar 

  5. Brox, J.H., Killie, J.E., Gunnes, S., and Nordoy, A. (1981)Thromb. Haemostas 3, 604–611.

    Google Scholar 

  6. Lorenz, R., Spengler, V., Fisher, S., Duhn, J., and Weber, P.C. (1983)Circulation 67, 504–511.

    PubMed  CAS  Google Scholar 

  7. Ahmed, A.A., and Holub, B.J. (1984)Lipids 19, 617–624.

    Article  PubMed  CAS  Google Scholar 

  8. Nordoy, A., Lagarde, M., and Renaud, S. (1984)Eur. J. Clin. Invest. 14, 339–345.

    PubMed  CAS  Google Scholar 

  9. Kondo, T., Ogawa, K., Satake, T., Kitazawa, M., TakI, K., Sugiyana, S., and Ozawa, T. (1986)Clin. Cardiol. 9, 413–416.

    Article  PubMed  CAS  Google Scholar 

  10. Watson, S.P., Reep, B., McConnell, R.T., and Lapetina, E.G. (1985)Biochem. J. 226, 831–837.

    PubMed  CAS  Google Scholar 

  11. Broekman, M.J., Ward, J.W., and Marcus, A.J. (1980)J. Clin. Invest. 66, 275–283.

    PubMed  CAS  Google Scholar 

  12. Berridge, M.J., and Irvine, R.F. (1984)Nature 312, 315–321.

    Article  PubMed  CAS  Google Scholar 

  13. Nishizuka, Y. (1986)Science 233, 305–312.

    Article  PubMed  CAS  Google Scholar 

  14. Billah, M.M., Lapetina, E.G., and Cuatrecasas, P. (1979)Biochem. Biophys. Res. Commun. 90, 92–98.

    Article  PubMed  CAS  Google Scholar 

  15. Brass, L.F., and Laposata, M. (1987)Biochem. Biophys. Res. Commun. 142, 7–14.

    Article  PubMed  CAS  Google Scholar 

  16. Smaal, E.B., Nicolay, K., Mandersloot, J.G., de Gier, J., and de Kruijff (1987)Biochim. Biophys. Acta 897, 453–466.

    Article  PubMed  CAS  Google Scholar 

  17. Kroll, M.H., Zaboico, G.B., and Schafer, A.I. (1989)J. Cell Physiol. 139, 558–564.

    Article  PubMed  CAS  Google Scholar 

  18. Melchert, H.-V., Limsathayourat, N., Mihajilovic, J., Eichberg, W., Thefeld, W., and Roftka, H. (1987)Atherosclerosis 65, 159–166.

    Article  PubMed  CAS  Google Scholar 

  19. Jacobsen, B.K., Trygg, K., Mjermann, I., Thomassen, M.S., Real, C., and Norum, K.R. (1983)Am. J. Clin. Nutr. 38, 906–913.

    PubMed  CAS  Google Scholar 

  20. Mustard, J.F., Perry, D.W., Ardlie, N.G., and Packham, M.A. (1972)Br. J. Haematol. 22, 193–204.

    PubMed  CAS  Google Scholar 

  21. Bligh, D.G., and Dyer, W.J. (1959)Can. J. Biochem. Physiol. 37, 911–917.

    PubMed  CAS  Google Scholar 

  22. Boukhchacke, D., and Lagarde, M. (1982)Biochim. Biophys. Acta 713, 386–392.

    Google Scholar 

  23. Salmon, J.A., and Flower, R.J. (1982)Methods Enzymol. 86, 477–493.

    PubMed  CAS  Google Scholar 

  24. Mitchell, K.T., Ferrell, J.E., Jr., and Huestis, W.H. (1986)Anal. Biochem. 158, 447–453.

    Article  PubMed  CAS  Google Scholar 

  25. Srivastava, K.C. (1985)Prost. Leuk. Med. 17, 319–327.

    Article  CAS  Google Scholar 

  26. Rao, G.H.R., Radha, E., and White, J.G. (1983)Biochem. Biophys. Res. Commun. 117 549–555.

    Article  PubMed  CAS  Google Scholar 

  27. Smith, D.L., Willis, A.L., Nguyen, N., Conner, D., Zahkedi, S., and Fulks, J. (1989)Lipids 24, 70–75.

    Article  PubMed  CAS  Google Scholar 

  28. Croset, M., Guichardart, M., and Lagarde, M. (1988)Biochim. Biophys. Acta 961, 252–269.

    Google Scholar 

  29. Fischer, S., von Schacky, C., Siess, W., Strasser, T.H., and Weber, P.C. (1984)Biochem. Biophys. Res. Commun. 120 907–918.

    Article  PubMed  CAS  Google Scholar 

  30. Chen, Z.M., Cerletti, C., de Gaetano, G., and Bertelé, V. (1987)Biochem. Biophys. Res. Commun. 149, 1193–1199.

    Article  PubMed  CAS  Google Scholar 

  31. Silver, M.J., Smith, J.B., Ingerman, C., and Kocsis, J.J. (1973)Prostaglandins 4, 863–875.

    Article  PubMed  CAS  Google Scholar 

  32. Spector, A.A. (1986)Methods Enzymol. 128, 320–329.

    Article  PubMed  CAS  Google Scholar 

  33. Hoak, J.C., Spector, A.A., Fry, G.L., and Barnes, B.C. (1972)Blood 40, 16–22.

    PubMed  CAS  Google Scholar 

  34. Corey, E.J., Shih, C., and Cashman, J.R. (1983)Proc. Natl. Acad. Sci. USA. 80, 3581–3584.

    Article  PubMed  CAS  Google Scholar 

  35. Dratewka-Kos, E., Tinker, D.O., and Kindl, B. (1985)Biochem. Cell Biol. 644, 906–913.

    Google Scholar 

  36. Swann, P.G., Venton, D.L., and LeBreton, G.C. (1988)FEBS Lett. 243, 244–246.

    Article  Google Scholar 

  37. Croset, M., Sala, A., Folco, G., and Lagarde, M. (1988)Biochem. Pharm. 37, 1275–1280.

    Article  PubMed  CAS  Google Scholar 

  38. Watanabe, T., Narumiya, S., Shimizu, T., and Hayaishi, O. (1982)J. Biol. Chem. 257, 14847–14853.

    PubMed  CAS  Google Scholar 

  39. Trist, D.G., Collins, B.A., Wood, J., Kelly, M.G., and Robertson, A.D. (1989)Br. J. Pharmacol. 96, 301–306.

    PubMed  CAS  Google Scholar 

  40. Spence, S., and Houslay, M.D. (1989) Abstract fromBiology of Cellular Transducing Signals '89, Washington, DC, May 1989.

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Gaudette, D.C., Holub, B.J. Albumin-bound docosahexaenoic acid and collagen-induced human platelet reactivity. Lipids 25, 166–169 (1990). https://doi.org/10.1007/BF02544332

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  • DOI: https://doi.org/10.1007/BF02544332

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