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Effects of omega-3 fatty acids on cytokines and adhesion molecules

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Abstract

The dietary intake of omega-3 (n-3) polyunsaturated fatty acids has emerged, over the past 20 years, as an important way to modify cardiovascular risk. This likely occurs through beneficial effects at all stages in the natural history of vascular disease, from the inception of atherosclerotic lesions, to their growth and acute complications (plaque rupture in most instances), up to protection of myocardium from the consequences of ensuing acute myocardial ischemia. This review specifically focuses on the modulating effects of n-3 fatty acids on biologic events involved in early atherogenesis, including important properties of these natural substances on endothelial expression of adhesion molecules and cytokines, processes collectively denoted as “endothelial activation.” By decreasing the endothelial responsiveness to proinflammatory and proatherogenic stimuli, n-3 fatty acids act on molecular events not targeted by any other drugs or interventions, and thereby complementary to those of already implemented pharmacologic treatments.

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References and Recommended Reading

  1. De Caterina R, Zampolli A: n-3 fatty acids: antiatherosclerotic effects. Lipids 2001, 36:S69-S78.

    Article  PubMed  Google Scholar 

  2. Davilgus M, Stamler J, Orencia A, et al.: Fish consumpion and the 30-year risk of fatal myocardial inarction. N Engl J Med 1997, 336:1046–1053.

    Article  Google Scholar 

  3. Albert C, Campos H, Stampfer M, et al.: Blood levels of long-chain n-3 fatty acids and the riesk of sudden death. N Engl J Med 2002, 346:1113–1118.

    Article  PubMed  CAS  Google Scholar 

  4. Kris-Etherton P, Harris W, Appel L, for the AHA Nutrition Committee: Omega-3 fatty acids and cardiovascular disease—new recommendations from the American Heart Association. Arterioscler Thromb Vasc Biol 2003, 23:151–152.

    Article  PubMed  CAS  Google Scholar 

  5. Middaugh J: Cardiovascular death among Alaskan natives 1980–1986. Am J Public Health 1990, 80:282–285.

    Article  PubMed  CAS  Google Scholar 

  6. Newman W, Middaugh J, Propst M, Rogers D: Atherosclerosis in Alaskan natives and non-natives. Lancet 1993, 341:1056–1057.

    Article  PubMed  CAS  Google Scholar 

  7. Sacks F, Stone P, Gibson C, et al.: Controlled trial of fish oil for regression of human coronary atherosclerosis. HARP Research Group. J Am Coll Cardiol 1995, 25:234–237.

    Article  Google Scholar 

  8. von Shacky C, Angerer P, Kothny W, et al.: The effect of dietary omega-3 fatty acids on coronary atherosclerosis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 1999, 130:554–562.

    Google Scholar 

  9. Angerer P, Kothny W, Stork S, von Schacky C: Effect of dietary supplementation with omega-3 fatty acids on progression of atherosclerosis in carotid arteries. Cardiovasc Res 2002, 54:183–190.

    Article  PubMed  CAS  Google Scholar 

  10. Angerer P, von Shacky C: n-3 polyunsaturated fatty acids and the cardiovascular system. Curr Opin Lipidol 2000, 11:57–63.

    Article  PubMed  CAS  Google Scholar 

  11. Eritsland J, Arnesen H, Gronseth K, et al.: Effect of supplementation with n-3 fatty acids on grft patency in patients undergoing coronary artery bypass operation. Results from the SHOT study [abstract 351]. Eur Heart J 1994, 15:29.

    Google Scholar 

  12. Slack J, Pinkerton C, Van Tassel J: Can oral fish oil supplement minimize re-stenosis after percutaneous transluminal angioplasty? [abstract]. J Am Coll Cardiol 1987, 9:64.

    Google Scholar 

  13. Dehmer GJ, Popma JJ, van den Berg EK, et al.: Reduction in the rate of early restenosis after coronary angioplasty by a diet supplemented with n-3 fatty acids. N Engl J Med 1988, 241:733–740.

    Article  Google Scholar 

  14. Grigg L, Kay T, Valentine P, et al.: Determinants of restenosis and lack of effect of dietary supplementation with eicosapentaenoic acid on the incidence of coronary artery restenosis after angioplasty. J Am Coll Cardiol 1989, 13:665–672.

    Article  PubMed  CAS  Google Scholar 

  15. Milner M, Gallino R, Leffingwell A, et al.: Usefulness of fish oil supplements in preventing clinical evidence of restenosis after percutaneous transluminal coronary angioplasty. Am J Cardiol 1989, 64:294–299.

    Article  PubMed  CAS  Google Scholar 

  16. Reis G, Boucher T, Sipperly M, et al.: Randomised trial of fish oil for prevention of restenosis after coronary angioplasty. Lancet 1989, 11:177–181.

    Article  Google Scholar 

  17. Nye E, Ilsley C, Ablett M, et al.: Effect of eicosapentaenoic acid on restenosis rate, clinical course and blood lipids in patients after percutaneous transluminal coronary angioplasty. Aust NZ J Med 1990, 20:549–552.

    CAS  Google Scholar 

  18. Bairati I, Roy L, Meyer F: Double-blind, randomized, controlled trial of fish oil supplements in prevention of recurrence of stenosis after coronary angioplasty. Circulation S-I 1992, 85:950–956.

    CAS  Google Scholar 

  19. Kaul U, Saghvi S, Bahl V, et al.: Fish oil supplements for prevention of restenosis after coronary angioplasty. Int J Cardiol 1992, 35:87–93.

    Article  PubMed  CAS  Google Scholar 

  20. Franzen D, Schannwell M, Oette K, Hopp H: A prospective, randomized, and double-blind trial on the effect of fish oil on the incidence of restenosis following PTCA. Cathet Cardiovasc Diagn 1993, 28:301–310.

    Article  PubMed  CAS  Google Scholar 

  21. Bellamy C, Schofield P, Faragher E, Ramsdale D: Can supplementation with omega-3 polyunsaturated fatty acids reduce coronary angioplasty restenosis rate? Eur Heart J 1992, 3:1626–1631.

    Google Scholar 

  22. Leaf A, Jorgensen M, Jacobs A, et al.: Do fish oils prevent restenosis after coronary angioplasty? Circulation S-I 1994, 90:2248–2257.

    CAS  Google Scholar 

  23. Cairns J, Gill J, Morton B, et al., for the EMPAR Collaborators: Fish oils and low-molecular-weight heparin for the reduction of restenosis after percutaneous transluminal coronary angioplasty. The EMPAR Study. Circulation S-I 1996, 94:1553–1560.

    CAS  Google Scholar 

  24. Maresta A, Balduccelli M, Varani E, et al.: Prevention of postcoronary angioplasty restenosis by omega-3 fatty acids: main results of the Esapent for Prevention of Restenosis Italian Study (ESPRIT). Am Heart J 2002, 143:1–10.

    Article  Google Scholar 

  25. De Caterina R, Gimbrone MA Jr: Leukocyte-endothelial interactions and the pathogenesis of atherosclerosis. In n-3 Fatty Acids—Prevention and Treatment in Vascular Disease. Edited by Kristensen SD, Schmidt EB, De Caterina R, Endres S. London: Springer Verlag; 1995:9–24.

    Google Scholar 

  26. Li H, Cybulsky MI, Gimbrone MA Jr, Libby P: An atherogenic diet rapidly induces VCAM-1, a cytokine-regulatable mononuclear leukocyte adhesion molecule, in rabbit aortic endothelium. Arterioscler Thromb 1993, 13:197–204.

    PubMed  Google Scholar 

  27. Cybulsky MJ, Iiyama K, Li H, et al.: A major role for VCAM-1, but not ICAM-1, in early atherosclerosis. J Clin Invest 2001, 107:1255–1262.

    Article  PubMed  CAS  Google Scholar 

  28. Libby P: Inflammation in atherosclerosis. Nature 2002, 420:866–874.

    Article  CAS  Google Scholar 

  29. Libby P: Vascular biology of atherosclerosis: overview and state of the art. Am J Cardiol 2003, 91(Suppl):3A-6A.

    Article  PubMed  CAS  Google Scholar 

  30. De Caterina R, Zampolli A: From asthma to atherosclerosis—5-lipoxygenase, leukotrienes, and inflammation. N Engl J Med 2004, 350:4–7.

    Article  PubMed  Google Scholar 

  31. De Caterina R, Cybulsky MI, Clinton SK, et al.: The omega-3 fatty acid docosahexaenoate reduces cytokine-induced expression of pro-atherogenic and pro-inflammatory proteins in human endothelial cells. Arterioscler Thromb 1994, 14:1829–1836.

    PubMed  Google Scholar 

  32. De Caterina R, Cybulsky M, Clinton S, et al.: Omega-3 fatty acids and endothelial leukocyte adhesion molecules. Prostagl Leukotr Ess Fatty Acids 1995, 52:191–195.

    Article  Google Scholar 

  33. Weber C, Erl W, Pietsch A, et al.: Docosahexaenoic acid selectively attenuates induction of vascular cell adhesion molecule-1 and subsequent monocytic cell adhesion to human endothelial cells stimulated by tumor necrosis factor-alpha. Arterioscler Thromb Vasc Biol 1995, 15:622–628.

    PubMed  CAS  Google Scholar 

  34. Collins T: Endothelial nuclear factor-kB and the initiation of the atherosclerotic lesion. Lab Invest 1993, 68:499–508.

    PubMed  CAS  Google Scholar 

  35. Collins T, Read M, Neish A, et al.: Transcriptional regulation of endothelial cell adhesion molecules: NF-kB and cytokineinducible enhancers. FASEB J 1995, 9:899–909.

    PubMed  CAS  Google Scholar 

  36. Kang JX, Wang J, Wu L, Kang ZB: Transgenic mice: fat-1 mice convert n-6 to n-3 fatty acids. Nature 2004, 427:504.

    Article  PubMed  CAS  Google Scholar 

  37. De Caterina R, Bernini W, Carluccio M, et al.: Structural requirements for inhibition of cytokine-induced endothelial activation by unsaturated fatty acids. J Lipid Res 1998, 39:1062–1070.

    PubMed  Google Scholar 

  38. Carluccio M, Massaro M, Bonfrate C, et al.: Oleic acid inhibits endothelial activation—a direct vascular antiatherogenic mechanism of a nutritional component in the Mediterranean diet. Arterioscler Thromb Vasc Biol 1999, 19:220–228.

    PubMed  CAS  Google Scholar 

  39. De Caterina R, Libby P, Peng HB, et al.: Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines. J Clin Invest 1995, 96:60–68.

    PubMed  Google Scholar 

  40. Massaro M, Basta G, Lazzerini G, et al.: Quenching of intracellular ROS generation as a mechanism for oleate-induced reduction of endothelial activation and early atherogenesis. Thromb Haemost 2002, 88:335–344.

    PubMed  CAS  Google Scholar 

  41. Dyerberg J, Bang HO, Stofferson E, et al.: Eicosapentaenoic acid and prevention of thrombosis and atherosclerosis. Lancet 1978, 2:117–119.

    Article  PubMed  CAS  Google Scholar 

  42. Endres S, Ghorbani R, Kelley VE: The effect of dietary supplementation with n-3 polyunsaturated fatty acid on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells. N Engl J Med 1989, 320:265–271.

    Article  PubMed  CAS  Google Scholar 

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  1. Institute of Cardiology, “G. d’Annunzio”, University - Chieti, C/o Ospedale S. Camillo de Lellis, Via Forlanini 50, 66100, Chieti, Italy

    Raffaele De Caterina MD, PhD

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  1. Raffaele De Caterina MD, PhD
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  2. Rosalinda Madonna MD, PhD
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  3. Marika Massaro DBiol, PhD
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De Caterina, R., Madonna, R. & Massaro, M. Effects of omega-3 fatty acids on cytokines and adhesion molecules. Curr Atheroscler Rep 6, 485–491 (2004). https://doi.org/10.1007/s11883-004-0090-x

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