PDF herunterladen
Semin Thromb Hemost 2013; 39(01): 025-032
DOI: 10.1055/s-0032-1333309
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Effects of Omega-3 Polyunsaturated Fatty Acids on Platelet Function in Healthy Subjects and Subjects with Cardiovascular Disease

Bradley J. McEwen
1   Northern Blood Research Centre, Kolling Institute of Medical Research, University of Sydney, New South Wales, Australia
2   Department of Haematology and Transfusion Medicine, Royal North Shore Hospital, St Leonards, New South Wales, Australia
,
Marie-Christine Morel-Kopp
1   Northern Blood Research Centre, Kolling Institute of Medical Research, University of Sydney, New South Wales, Australia
2   Department of Haematology and Transfusion Medicine, Royal North Shore Hospital, St Leonards, New South Wales, Australia
,
Walter Chen
1   Northern Blood Research Centre, Kolling Institute of Medical Research, University of Sydney, New South Wales, Australia
2   Department of Haematology and Transfusion Medicine, Royal North Shore Hospital, St Leonards, New South Wales, Australia
,
Geoffrey H. Tofler
3   Department of Cardiology, Royal North Shore Hospital, St Leonards, New South Wales, Australia
,
Christopher M. Ward
1   Northern Blood Research Centre, Kolling Institute of Medical Research, University of Sydney, New South Wales, Australia
2   Department of Haematology and Transfusion Medicine, Royal North Shore Hospital, St Leonards, New South Wales, Australia
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
17. Januar 2013 (online)

    Lizenzen und Reprints

Abstract

Hyperactivation and aggregation of platelets play a major role in thrombosis and hemostasis. The aims of this study were to investigate the effects of omega-3 polyunsaturated fatty acids (PUFAs) on platelet function. Light transmission aggregometry and flow cytometric analyses of platelet activation and platelet–leukocyte aggregates were determined at baseline and after 4 weeks of omega-3 (docosahexaenoic acid 520 mg and eicosapentaenoic acid 120 mg) supplementation. In total, 40 healthy subjects and 16 patients with a history of cardiovascular disease (CVD) completed the study. In healthy subjects, omega-3 PUFA significantly reduced adenosine diphosphate (ADP)–induced (maximum amplitude, 77.0% ± 3.2% vs. 71.6% ± 3.4%, p = 0.036; maximum slope, 86.3 ± 1.8 vs. 80.7 ± 2.1, p = 0.014) and adrenaline-induced platelet aggregation (maximum slope, 42.8 ± 2.7 vs. 37.4 ± 3.0, p = 0.013; lag time, 00:21 ± 00:02 vs. 00:31 ± 00:03 s, p = 0.002). Omega-3 PUFA also reduced P-selectin expression (40.5% ± 2.9% vs. 34.4% ± 2.4%, p = 0.049) on platelets and platelet–monocyte aggregates (38.5% ± 2.6% vs. 31.4% ± 2.5%, p = 0.022) after activation with ADP 0.5 µM. There were fewer changes in platelet aggregation and activation found in subjects with CVD. Nevertheless, there was a reduction in the slope of arachidonic acid–induced platelet aggregation (13.21 ± 6.41 vs. 4.88 ± 3.01, p = 0.009) and increased lag time for U46619 (00:16 ± 00:00 vs. 00:29 ± 00:07 s, p = 0.018) induced platelet aggregation. Thus, 4-week supplementation of 640 mg omega-3 PUFA reduced measures of platelet aggregation and activation in healthy subjects but effects were less evident in patients with existing CVD. Our findings support the recommendation that the omega-3 PUFA dose be higher in CVD than among healthy subjects.

Keywords

cardiovascular disease - omega-3 PUFA - platelet activation - platelet aggregation - thrombosis
 

  • References

  • 1 Roger VL, Go AS, Lloyd-Jones DM , et al; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics—2012 update: a report from the American Heart Association. Circulation 2012; 125 (1) e2-e220
    CrossrefPubMedSuche in Google Scholar
  • 2 Begonja AJ, Gambaryan S, Geiger J , et al. Platelet NAD(P)H-oxidase-generated ROS production regulates alphaIIbbeta3-integrin activation independent of the NO/cGMP pathway. Blood 2005; 106 (8) 2757-2760
    CrossrefPubMedSuche in Google Scholar
  • 3 McNicol A, Israels SJ. Platelet dense granules: structure, function and implications for haemostasis. Thromb Res 1999; 95 (1) 1-18
    CrossrefPubMedSuche in Google Scholar
  • 4 Davì G, Patrono C. Platelet activation and atherothrombosis. N Engl J Med 2007; 357 (24) 2482-2494
    CrossrefPubMedSuche in Google Scholar
  • 5 Ruggeri ZM. Platelets in atherothrombosis. Nat Med 2002; 8 (11) 1227-1234
    CrossrefPubMedSuche in Google Scholar
  • 6 Blann AD, Lip GY. Virchow's triad revisited: the importance of soluble coagulation factors, the endothelium, and platelets. Thromb Res 2001; 101 (4) 321-327
    CrossrefPubMedSuche in Google Scholar
  • 7 Hechler B, Cattaneo M, Gachet C. The P2 receptors in platelet function. Semin Thromb Hemost 2005; 31 (2) 150-161
    Thieme ConnectPubMedSuche in Google Scholar
  • 8 Schulz C, Penz S, Hoffmann C , et al. Platelet GPVI binds to collagenous structures in the core region of human atheromatous plaque and is critical for atheroprogression in vivo. Basic Res Cardiol 2008; 103 (4) 356-367
    CrossrefPubMedSuche in Google Scholar
  • 9 Munnix IC, Cosemans JM, Auger JM, Heemskerk JW. Platelet response heterogeneity in thrombus formation. Thromb Haemost 2009; 102 (6) 1149-1156
    PubMedSuche in Google Scholar
  • 10 Shantsila E, Lip GY. The role of monocytes in thrombotic disorders. Insights from tissue factor, monocyte-platelet aggregates and novel mechanisms. Thromb Haemost 2009; 102 (5) 916-924
    PubMedSuche in Google Scholar
  • 11 Freedman JE, Loscalzo J. Platelet-monocyte aggregates: bridging thrombosis and inflammation. Circulation 2002; 105 (18) 2130-2132
    CrossrefPubMedSuche in Google Scholar
  • 12 Lippi G, Montagnana M, Salvagno GL , et al. Risk stratification of patients with acute myocardial infarction by quantification of circulating monocyte-platelet aggregates. Int J Cardiol 2007; 115 (1) 101-102
    CrossrefPubMedSuche in Google Scholar
  • 13 Sarma J, Laan CA, Alam S, Jha A, Fox KA, Dransfield I. Increased platelet binding to circulating monocytes in acute coronary syndromes. Circulation 2002; 105 (18) 2166-2171
    CrossrefPubMedSuche in Google Scholar
  • 14 Cattaneo M. Light transmission aggregometry and ATP release for the diagnostic assessment of platelet function. Semin Thromb Hemost 2009; 35 (2) 158-167
    Thieme ConnectPubMedSuche in Google Scholar
  • 15 Born GV. Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature 1962; 194: 927-929
    PubMedSuche in Google Scholar
  • 16 Michelson AD, Barnard MR, Krueger LA, Frelinger III AL, Furman MI. Evaluation of platelet function by flow cytometry. Methods 2000; 21 (3) 259-270
    CrossrefPubMedSuche in Google Scholar
  • 17 Michelson AD. Flow cytometry: a clinical test of platelet function. Blood 1996; 87 (12) 4925-4936
    PubMedSuche in Google Scholar
  • 18 Favaloro EJ. Clinical utility of the PFA-100. Semin Thromb Hemost 2008; 34 (8) 709-733
    Thieme ConnectPubMedSuche in Google Scholar
  • 19 Harrison P, Robinson M, Liesner R , et al. The PFA-100: a potential rapid screening tool for the assessment of platelet dysfunction. Clin Lab Haematol 2002; 24 (4) 225-232
    CrossrefPubMedSuche in Google Scholar
  • 20 Benatti P, Peluso G, Nicolai R, Calvani M. Polyunsaturated fatty acids: biochemical, nutritional and epigenetic properties. J Am Coll Nutr 2004; 23 (4) 281-302
    CrossrefPubMedSuche in Google Scholar
  • 21 Kris-Etherton PM, Harris WS, Appel LJ. Nutrition Committee. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Arterioscler Thromb Vasc Biol 2003; 23 (2) e20-e30
    CrossrefPubMedSuche in Google Scholar
  • 22 Marchioli R, Barzi F, Bomba E , et al; GISSI-Prevenzione Investigators. Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-Prevenzione. Circulation 2002; 105 (16) 1897-1903
    CrossrefPubMedSuche in Google Scholar
  • 23 Tavazzi L, Maggioni AP, Marchioli R , et al; Gissi-HF Investigators. Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet 2008; 372 (9645) 1223-1230
    CrossrefPubMedSuche in Google Scholar
  • 24 Singer P, Wirth M. Can n-3 PUFA reduce cardiac arrhythmias? Results of a clinical trial. Prostaglandins Leukot Essent Fatty Acids 2004; 71 (3) 153-159
    CrossrefPubMedSuche in Google Scholar
  • 25 Bays HE, Tighe AP, Sadovsky R, Davidson MH. Prescription omega-3 fatty acids and their lipid effects: physiologic mechanisms of action and clinical implications. Expert Rev Cardiovasc Ther 2008; 6 (3) 391-409
    CrossrefPubMedSuche in Google Scholar
  • 26 Calder PC. The role of marine omega-3 (n-3) fatty acids in inflammatory processes, atherosclerosis and plaque stability. Mol Nutr Food Res 2012; 56 (7) 1073-1080
    CrossrefPubMedSuche in Google Scholar
  • 27 Mori TA, Watts GF, Burke V, Hilme E, Puddey IB, Beilin LJ. Differential effects of eicosapentaenoic acid and docosahexaenoic acid on vascular reactivity of the forearm microcirculation in hyperlipidemic, overweight men. Circulation 2000; 102 (11) 1264-1269
    CrossrefPubMedSuche in Google Scholar
  • 28 Din JN, Newby DE, Flapan AD. Omega 3 fatty acids and cardiovascular disease—fishing for a natural treatment. BMJ 2004; 328 (7430) 30-35
    CrossrefPubMedSuche in Google Scholar
  • 29 Harris WS, Kris-Etherton PM, Harris KA. Intakes of long-chain omega-3 fatty acid associated with reduced risk for death from coronary heart disease in healthy adults. Curr Atheroscler Rep 2008; 10 (6) 503-509
    CrossrefPubMedSuche in Google Scholar
  • 30 Surette ME. The science behind dietary omega-3 fatty acids. CMAJ 2008; 178 (2) 177-180
    CrossrefPubMedSuche in Google Scholar
  • 31 Gebauer SK, Psota TL, Harris WS, Kris-Etherton PM. n-3 fatty acid dietary recommendations and food sources to achieve essentiality and cardiovascular benefits. Am J Clin Nutr 2006; 83 (6) (Suppl): 1526S-1535S
    PubMedSuche in Google Scholar
  • 32 National Heart Foundation of Australia. Position Statement: Fish, Fish Oils, n-3 Polyunsaturated Fatty Acids and Cardiovascular Health. Canberra, Australian Capital Territory, Australia: National Heart Foundation of Australia; 2008
    Suche in Google Scholar
  • 33 Mackay I, Ford I, Thies F, Fielding S, Bachoo P, Brittenden J. Effect of Omega-3 fatty acid supplementation on markers of platelet and endothelial function in patients with peripheral arterial disease. Atherosclerosis 2012; 221 (2) 514-520
    CrossrefPubMedSuche in Google Scholar
  • 34 Serebruany VL, Miller M, Pokov AN , et al. Early impact of prescription Omega-3 fatty acids on platelet biomarkers in patients with coronary artery disease and hypertriglyceridemia. Cardiology 2011; 118 (3) 187-194
    CrossrefPubMedSuche in Google Scholar
  • 35 Cohen MG, Rossi JS, Garbarino J , et al. Insights into the inhibition of platelet activation by omega-3 polyunsaturated fatty acids: beyond aspirin and clopidogrel. Thromb Res 2011; 128 (4) 335-340
    CrossrefPubMedSuche in Google Scholar
  • 36 Doenyas-Barak K, Berman S, Abu-Hamad R, Golik A, Rahimi-Levene N, Efrati S. N-3 fatty acid supplementation to routine statin treatment inhibits platelet function, decreases patients' daytime blood pressure, and improves inflammatory status. Eur J Clin Pharmacol 2012; 68 (8) 1139-1146
    CrossrefPubMedSuche in Google Scholar
  • 37 Undas A, Brummel-Ziedins KE, Mann KG. Antithrombotic properties of aspirin and resistance to aspirin: beyond strictly antiplatelet actions. Blood 2007; 109 (6) 2285-2292
    CrossrefPubMedSuche in Google Scholar
  • 38 Din JN, Harding SA, Valerio CJ , et al. Dietary intervention with oil rich fish reduces platelet-monocyte aggregation in man. Atherosclerosis 2008; 197 (1) 290-296
    CrossrefPubMedSuche in Google Scholar
  • 39 Nomura S, Kanazawa S, Fukuhara S. Effects of eicosapentaenoic acid on platelet activation markers and cell adhesion molecules in hyperlipidemic patients with Type 2 diabetes mellitus. J Diabetes Complications 2003; 17 (3) 153-159
    CrossrefPubMedSuche in Google Scholar
  • 40 Marwali MR, Hu CP, Mohandas B , et al. Modulation of ADP-induced platelet activation by aspirin and pravastatin: role of lectin-like oxidized low-density lipoprotein receptor-1, nitric oxide, oxidative stress, and inside-out integrin signaling. J Pharmacol Exp Ther 2007; 322 (3) 1324-1332
    CrossrefPubMedSuche in Google Scholar