Platelet — Vessel Wall Interactions in Individuals who Smoke Cigarettes

  • John J. Murray
  • Jacek Nowak
  • John A. Oates
  • Garret A. FitzGerald
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 273)


Sudden cardiac death is the most frequent cause of mortality in industrialized societies accounting for the majority of the over 325,000 smoking-related deaths each year in the United States1. The strong link between cigarette smoking and the platelet-modulated syndrome of sudden cardiac death2,3 implicates smoking as a cause of platelet activation. Consistent with this hypothesis of a direct activation of platelets is that platelet turnover appears to be accelerated in apparently healthy smokers4,5. However, an enhanced turnover of platelets may be the result of their increased clearance following membrane alterations after interaction with a damaged vasculature and conversely, thrombosis has been shown to occur in vivo without evidence of increased turnover6–8. Thus, an enhanced platelet turnover in smokers may not necessarily reflect a direct activation of platelets in vivo. In fact, ex vivo aggregation has been found to be either increased9,10, unchanged4,12–14 or significantly decreased15,16 in chronic smokers.


Cigarette Smoking Platelet Activation Urinary Metabolite Aspirin Treatment Chronic Smoker 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    W. B. Kannel. Update on the role of cigarette smoking in coronary artery disease. Am. Heart J. 101:319 (1981).PubMedCrossRefGoogle Scholar
  2. 2.
    M. J. Davies and A. Thomas. Thrombosis and acute coronary artery lesions in sudden cardiac ischemic death. N. Engl. J. Med. 310:1137 (1984).PubMedCrossRefGoogle Scholar
  3. 3.
    E. Falk. Unstable angina with fatal outcome: dynamic coronary thrombosis leading to infarction and/or sudden death. Circulation 71:699 (1985).PubMedCrossRefGoogle Scholar
  4. 4.
    J. F. Mustard and E. A. Murphy. Effect of smoking on blood coagulation and platelet survival in man. Br. Med. J. 1:846 (1963).PubMedCrossRefGoogle Scholar
  5. 5.
    V. Fuster, J. H. Cheseboro, R. L. Frye, and L. R. Elveback. Platelet survival and the development of coronary artery disease in the young adult: Effects of cigarette smoking, strong family history and medical therapy. Circulation 63:546 (1981).PubMedCrossRefGoogle Scholar
  6. 6.
    B. L. Kinlough-Rathbone, M. A. Packam and J. F. Mustard. Vessel injury, platelet-adherence and platelet survival. Arteriosclerosis 3:529 (1983).PubMedCrossRefGoogle Scholar
  7. 7.
    P. D. Winocour, M. Cattaneo, D. Somers, M. Richardson, R. L. Kinlough-Rathbone and J. F. Mustard. Platelet survival and thrombosis. Arteriosclerosis 2:458 (1982).PubMedCrossRefGoogle Scholar
  8. 8.
    H. M. Graves, R. L. Kinlough-Rathbone, M. Richardson, L. Jorgensen, S. Moore and J. F. Mustard. Thrombin generation and fibrosis formation following injury to rabbit neointima: Studies of vessel wall reactivity and platelet survival. Lab. Invest. 46:605 (1982).Google Scholar
  9. 9.
    P. Ashby, A. M. Dalby and J. H. Millar. Smoking and platelet stickiness. Lancet 2:158 (1965).CrossRefGoogle Scholar
  10. 10.
    R. I. Hawkins. Smoking, platelets and thrombosis. Nature 236:450 (1972).PubMedCrossRefGoogle Scholar
  11. 11.
    K. G. Schmidt and J. W. Rasmussen. Acute platelet activation-induced by smoking: in vivo and ex vivo studies in man. Throm. Haemost. 51:279 (1984).Google Scholar
  12. 12.
    L. E. Murchison and T. Fyfe. Effects of cigarette smoking on serumlipids, blood glucose and platelet adhesiveness. Lancet 2:182 (1966).PubMedCrossRefGoogle Scholar
  13. 13.
    W. Siess, R. Lorenz, P. Roth and P. C. Weber. Plasma catecholamines, platelet aggregation and associated thromboxane formation after physical exercise, smoking and norepinephrine infusion. Circulation 66:41 (1982).CrossRefGoogle Scholar
  14. 14.
    W. R. Rogers, R. L. Bass III, D. E. Johnson, A. W. Kruski, C. A. McMahon, M. M. Montiel, G. E. Mott, R. L. Wilbur and H. C. McGill, Jr. Atherosclerosis-related responses to cigarette smoking in the baboon. Circulation 61:1188 (1980).PubMedGoogle Scholar
  15. 15.
    A. Mansouri and C. A. Perry. Inhibition of platelet ADP and serotonin release by carbon monoxide. Experientia 40:515 (1984).PubMedCrossRefGoogle Scholar
  16. 16.
    T. W. Meade, M. V. Vicekers, S. G. Thompson, Y. Styirling, A. P. Haines and G. J. Miller. Epidemiological characteristics of platelet aggregability. Br. Med. J. 290:428 (1985).CrossRefGoogle Scholar
  17. 17.
    B. Samuelsson. The role of prostaglandin endoperoxides and thromboxanes as bioregulators. in: “Proceedings of the Intrascience Symposium on the New Biochemistry of Prostaglandins and Thromboxanes.” N. Kharsch and J. Fried, eds., Publisher New York Academic Press, Santa Monica, CA (1977).Google Scholar
  18. 18.
    F. Catella and G. A. FitzGerald. Paired analysis of urinary thromboxane B2 metabolites in humans. Throm. Research 47:647 (1987).CrossRefGoogle Scholar
  19. 19.
    D. J. Fitzgerald, F. Catella, L. Roy and G. A. Fitzgerald. Platelet activation in unstable coronary disease. N. Engl. J. Med. 315:983 (1986).PubMedCrossRefGoogle Scholar
  20. 20.
    D. J. Fitzgerald, J. Doran, E. K. Jackson and G. A. FitzGerald. Coronary vascular occlusion mediated through thromboxane A2-endoperoxide receptor activation in vivo. J. Clin. Invest. 77:496 (1986).PubMedCrossRefGoogle Scholar
  21. 21.
    I. Asmussen and K. Kjeldsen. Intimal ultrastructure of human umbilical arteries. Observations on arteries from newborn children of smoking and nonsmoking mothers. Circ. Res. 36:579 (1975).PubMedGoogle Scholar
  22. 22.
    H. K. Thomsen. Carbon monoxide-induced atherosclerosis in primates. Atherosclerosis 20:233 (1974).PubMedCrossRefGoogle Scholar
  23. 23.
    P. Ribeiro, R. Walesby, S. Edmonson, A. V. Jadhar, I. Traynor, C. M. Oakley and G. R. Thompson. Collagen content of atherosclerotic arteries is higher in smokers than in nonsmokers. Lancet 2:107 (1983).Google Scholar
  24. 24.
    J. H. Reinders, H-J. M. Brinkman, J. A. van Mourik and P. G. deGroot. Cigarette smoke impairs endothelial cell prostacyclin production. Arteriosclerosis 6:15 (1986).PubMedCrossRefGoogle Scholar
  25. 25.
    T. Sonnenfeld and Å. Wennmalm. Inhibition by nicotine of the formation of prostacyclin-like activity in rabbit and human vascular tissue. Br. J. Pharmacol. 71:609 (1980).PubMedGoogle Scholar
  26. 26.
    J. L. Nadler, J. S. Velasco and R. Horton. Cigarette smoking inhibits prostacyclin formation. Lancet 1:248 (1983).Google Scholar
  27. 27.
    G. A. FitzGerald, B. Smith, A. K. Pedersen and A. R. Brash. Increased prostacyclin biosynthesis in patients with severe atherosclerosis and platelet activation. N. Engl. J. Med. 310:1065 (1984).PubMedCrossRefGoogle Scholar
  28. 28.
    I. A. G. Reilly, L. Roy and G. A. FitzGerald. Thromboxane biosynthesis is increased in systemic sclerosis with Raynaud’s phenomenon. Br.Med.J. 292:1087 (1986).CrossRefGoogle Scholar
  29. 29.
    J. J. Murray, J. Nowak, J. A. Oates and G. A. FitzGerald. Biosynthesis of thromboxane A2 and prostacyclin during chronic smoking and withdrawal in man. Clin. Res. 33:521A (1985).Google Scholar
  30. 30.
    I. A. G. Reilly and G. A. FitzGerald. Eicosanoid biosynthesis and platelet function with advancing age. Thrombosis Res. 41:545 (1986).CrossRefGoogle Scholar
  31. 31.
    G. A. Kyerematen, M. D. Damiano, B. H. Dvorchik and E. S. Vesell. Smoking-induced changes in nicotine disposition: Application of a new HPLC assay for nicotine and its metabolites. Clin. Pharmacol. Ther. 32:769 (1982).PubMedCrossRefGoogle Scholar
  32. 32.
    J.J. Murray, J. Nowak, J. A. Oates and G. A. FitzGerald. Platelet function during chronic smoking and withdrawal. Clin. Res. 33:350A (1985).Google Scholar
  33. 33.
    J. Nowak, J. J. Murray, J. A. Oates and G. A. Fitzgerald. Biochemical evidence of a chronic abnormality in platelet and vascular function in apparently healthy chronic cigarette smokers. Circulation 76:6 (1987).PubMedCrossRefGoogle Scholar
  34. 34.
    S. Fischer, C. Bernutz, H. Meier and P. C. Weber. Formation of prostacyclin and thromboxane in man as measured by the main urinary metabolites. Biochim. Biophys. Acta 876:194 (1986).PubMedGoogle Scholar
  35. 35.
    R. Lassila, H. W. Seyberth, A. Haspanen, H. W. Schweer, M. Koskenvuo and K. E. Laustiola. Vasoactive and atherogenic effects of cigarette smoking- a study of monozygotic twins discordant for smoking. Br. Med. J. 297:955 (1988).CrossRefGoogle Scholar
  36. 36.
    Å. Wennmalm. Smoking induced alterations in thromboxane biosynthesis: a population study. Presented at the Winter Prostaglandin Conference. Keystone, CO (1988).Google Scholar
  37. 37.
    S. E. Barrow, P. S. Ward. M. A. Sleightholm, J. M. Ritter and C. T. Dollery. Cigarette smoking: profiles of thromboxane- and prostacyclin-derived products in urine. Biochim. Biophys. Acta 993:121 (1989).PubMedCrossRefGoogle Scholar
  38. 38.
    G. A. FitzGerald, J. A. Oates, J. Hawiger, R. L. Maas, L. J. Roberts II, J. A. Lawson and A. R. Brash. Endogenous biosynthesis of prostacyclin and thromboxane and platelet function during administration of aspirin in man. J. Clin. Invest. 71:676 (1983).PubMedCrossRefGoogle Scholar
  39. 39.
    A. K. Pedersen, J. Nowak and G. A. FitzGerald. Slow administration of low dose aspirin:Enhanced inhibition of platelet cyclooxygenase. Circulation 72:772A (1985).CrossRefGoogle Scholar
  40. 40.
    G. A. FitzGerald, A. R. Brash, I. A. Blair and J. Lawson. Analysis of urinary metabolites of thromboxane and prostacyclin by negative ion-chemical ionization gas chromatography-mass spectrometry. Adv. Prostglandin Thromboxane Res. 15:87 (1985).Google Scholar
  41. 41.
    P. Hill and E. L. Wyner. Smoking and cardiovascular disease- effect of nicotine on the serum epinephrine and corticoids. Am. Heart J. 87:491 (1974).PubMedCrossRefGoogle Scholar
  42. 42.
    R. M. Pittilo, J. M. Clarke, D. Harris, I. J. Mackie, P. M. Rowles, S. J. Machin and N. Woolf. Cigarette smoking and platelet adhesion. Br. J. Haematol. 58:627 (1984).PubMedCrossRefGoogle Scholar
  43. 43.
    P. E. Cryer, M. W. Haymond, J. V. Santiago and S. D. Shah. Norepinephrine and epinephrine release and adrenergic mediation of smoking-associated hemodynamic and metabolic events. N. Engl. J. Med. 295:573 (1976).PubMedCrossRefGoogle Scholar
  44. 44.
    P. H. Levine. An acute effect of cigarette smoking on platelet function. A possible link between smoking and arterial thrombosis. Circulation 48:619 (1973).PubMedGoogle Scholar
  45. 45.
    J. J. Belch, B. M. McArdle, P. Burns, G. D. Lowe and C. D. Forbes. The effects of acute smoking on platelet behaviour, fibrinolysis haemarheology in habitual smokers. Thromb. Haemostasis 51:6 (1984).Google Scholar
  46. 46.
    T. Gordon, W. B. Kannel, D. McGee and T. R. Dawber. Death and coronary attacks in men giving up smoking. A report of the Framingham study. Lancet ii:1345 (1974).CrossRefGoogle Scholar
  47. 47.
    R. Doll and A. B. Hill. Mortality in relation to smoking: Ten years’ observation of British doctors. Br. Med. J. 1:1406 (1964).Google Scholar
  48. 48.
    L. Wilhelmsen. Coronary artery disease: Epidemiology of smoking and intervention studies of smoking. Am. Heart J. 115:242 (1988).PubMedCrossRefGoogle Scholar
  49. 49.
    L. Rosenberg, D. W. Kaufman, S. P. Helmrich and S. Shapiro. Risk of myocardial infarction after quitting smoking in men under 55 years of age. N. Engl. J. Med. 313:1511 (1985).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • John J. Murray
    • 1
  • Jacek Nowak
    • 1
  • John A. Oates
    • 1
  • Garret A. FitzGerald
    • 1
  1. 1.Division of Clinical Pharmacology Departments of Medicine and PharmacologyVanderbilt Medical CenterNashvilleUSA

Personalised recommendations