Platelets in the Pathogenesis of Atherosclerosis

  • Wolfgang Siess
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 273)


The major function of platelets is to maintain the hemostatic integrity of the blood vessel and to stop bleeding after injury. Platelets show different responses that can be studied separately in vitro, but that are closely linked during hemostasis in vivo: adhesion and shape change, aggregation and secretion. Many diverse substances can activate platelets, and platelets are very sensitive to these agents and react within seconds of exposure to these stimuli. The most important physiological stimuli are von Willebrand factor and collagen, which mediate platelet adhesion; thrombin, which is generated by the coagulation system; prostaglandin endoperoxides, thromboxane, and ADP, which are released from activated platelets; platelet-activating factor, which is liberated from stimulated neutrophils and macrophages, and catecholamines, which are present in the circulation and show high levels after stress and cigarette smoking.


Nitric Oxide Platelet Aggregation Platelet Activation Foam Cell Platelet Inhibition 


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  1. 1.
    Siess W. Molecular mechanisms of platelet activation. Physiol. Rev. 69:58–178 (1989).PubMedGoogle Scholar
  2. 2.
    Siess, W., Lapetina, E.G. Calcium primes protein kinase C in human platelets. Biochem. J. 255:309–318 (1988).PubMedGoogle Scholar
  3. 3.
    Siess W., Lapetina E.G. Platelet aggregation induced by α2-adrenoceptor- and protein kinase C activation: A novel synergism. Biochem. J. in press (1989).Google Scholar
  4. 4.
    Olbrich C., Siess W. Epinephrine and the Ca2+-ionophore A 23187 synergistically induce platelet aggregation without protein kinase C activation. FEBS Lett. 243:275–279 (1989).PubMedCrossRefGoogle Scholar
  5. 5.
    Friedman J., Stemerman M.D., Wenz B., Moore S., Gauldie J., Gent M., Tiell M.L., Spaet T.H. The effect of thrombocytopenia on experimental arteriosclerotic lesion formation in rabbits. J. Clin. Invest. 60:1191–1201 (1977).PubMedCrossRefGoogle Scholar
  6. 6.
    Schwartz C.J., Valente A.J., Kelley J.L., Sprague E.A., Edwards E.H. Thrombosis and the development of atherosclerosis: Rokitansky revisited. Semin. Thrombos. Hemostas. 14:189–195 (1988).CrossRefGoogle Scholar
  7. 7.
    Ross R. The pathogenesis of atherosclerosis — an update. N. Engl. J. Med. 314:488–500 (1986).PubMedCrossRefGoogle Scholar
  8. 8.
    Furchgott R.F., Zawadzki J.V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288:373–376 (1980).PubMedCrossRefGoogle Scholar
  9. 9.
    Palmer R.M., Ferrige A.G., Moncada S. Nitric oxide release accounts for the biological activity of endothelium- derived relaxing factor. Nature 327:524–526 (1987).PubMedCrossRefGoogle Scholar
  10. 10.
    Freiman P.C., Mitchell G.C., Heistad D.D., Armstrong M.L., Harrison D.G. Atherosclerosis impairs endothelium-dependent vascular relaxation to acetylcholine and thrombin in primates. Circ. Res. 58:783–789 (1986).PubMedGoogle Scholar
  11. 11.
    Radomski M.W., Palmer R.M.J., Moncada S. Endogenous nitric oxide inhibits human platelet adhesion to vascular endothelium. Lancet 2:1057–1058 (1987).PubMedCrossRefGoogle Scholar
  12. 12.
    Moncada S., Gryglewski R., Bunting S., Vane J.R. An enzyme isolated from arteries transforms prostaglandin endoper-oxides to an unstable substance that inhibits platelet aggregation. Nature 263:663–665 (1976).PubMedCrossRefGoogle Scholar
  13. 13.
    Radomski M.W., Palmer R.M.J., Moncada S. The antiaggregating properties of vascular endothelium: interaction between prostacyclin and nitric oxide. Br. J. Pharmacol. 92:639–646 (1987).PubMedGoogle Scholar
  14. 14.
    Brook G.J., Aviram M. Platelet lipoprotein interactions. Semin. Thrombos. Hemostas. 14:258–265 (1988).CrossRefGoogle Scholar
  15. 15.
    Shattil S.J., Anaya-Galindo R., Bennett J., Colman R.W., Cooper R.A. Platelet hypersensitivity induced by cholesterol incorporation. J. Clin. Invest. 55:636–643 (1975).PubMedCrossRefGoogle Scholar
  16. 16.
    Koller E., Koller F., Binder B.R. Purification and identification of the lipoprotein-binding proteins from human blood platelet membrane. J. Biol. Chem. 264:12412–12418 (1989).PubMedGoogle Scholar
  17. 17.
    Andrews H.E., Aitken J.W., Hassal D.G., Skinner V.O., Bruckdorfer K.R. Intracellular mechanisms in the activation of human platelets by low-density lipoproteins. Biochem. J. 242:559–564 (1987).PubMedGoogle Scholar
  18. 18.
    Block L.H., Knorr M., Vogt E., Locher R., Vetter W., Grosgurth P., Qiao B-Y., Pometta D., James R., Regenass M., Pletscher A. Low density lipoprotein causes general cellular activation with increased phosphatidylinositol turnover and lipoprotein catabolism. Proc. Natl. Acad. Sci. 85:885–889 (1988).PubMedCrossRefGoogle Scholar
  19. 19.
    Faggiotto A., Ross R., Harker L. Studies of hypercholesterolemia in the nonhuman primate. I. Changes that lead to fatty streak formation. Arteriosclerosis 4:323- (1984).PubMedCrossRefGoogle Scholar
  20. 20.
    Munro M.J., Cotran R. The pathogenesis of atherosclerosis: atherogenesis and inflammation. Lab. Invest. 58:249–261 (1988).PubMedGoogle Scholar
  21. 21.
    Sevitt S. Platelets and foam cells in the evolution of atherosclerosis. Atherosclerosis 61:107–115 (1986).PubMedCrossRefGoogle Scholar
  22. 22.
    Curtiss L.K., Black A.S., Takagi Y., Plow E.F. New mechanisms for foam cell generation in atherosclerosis lesions. J. Clin. Invest. 80:367–373 (1987).PubMedCrossRefGoogle Scholar
  23. 23.
    Mendelsohn M.E., Loscalzo J. Role of platelets in cholesterol ester formation by U-937 cells. J. Clin. Invest, 81:62–68 (1988).PubMedCrossRefGoogle Scholar
  24. 24.
    Larsen E., Celi A., Gilbert G.E., Furie B.C., Erban J.K., Bonfanti R., Wagner D.D., Furie B. PADGEM Protein: A receptor that mediates the interaction of activated platelets with neutrophils and monocytes. Cell 59:305–312 (1989).PubMedCrossRefGoogle Scholar
  25. 25.
    Sandberg H., Anderson L-O, Hoglund S. Isolation and characterization of lipid-protein particles containing platelet factor 3 released from human platelets. Biochem. J. 203:303–311 (1982).PubMedGoogle Scholar
  26. 26.
    Kruth H.S. Platelet mediated cholesterol accumulation in cultured aortic smooth muscle cells. Science 227:1243–1245 (1985).PubMedCrossRefGoogle Scholar
  27. 27.
    Kaplan K.L. Platelet granule proteins: localization and secretion. In Platelets in Biology and Pathology-2, J.L. Gordon (ed) Elsevier, Amsterdam p. 80–90 (1981).Google Scholar
  28. 28.
    Ross R. Platelet derived growth factor. Lancet 1:1179–1182 (1989).PubMedCrossRefGoogle Scholar
  29. 29.
    Usuki K., Heldin N-E., Miyazono K., Ishikawa F., Takaku F., Westermark B., Heldin C-H. Production of platelet-derived endothelial cell growth factor by normal and transformed human cells in culture. Proc. Natl. Acad. Sci. USA 86:7427–7431 (1989).PubMedCrossRefGoogle Scholar
  30. 30.
    Dyerberg J., Bang H.O. Hemostatic function and platelet polyunsaturated fatty acids in Eskimos. Lancet 2:433–435 (1979).PubMedCrossRefGoogle Scholar
  31. 31.
    Dyerberg J., Bang H.O., Stoffersen E., Moncada S., Vane J.R. Eicosapentaenoic acid and prevention of thombosis and atherosclerosis. Lancet 2:117–119 (1978).PubMedCrossRefGoogle Scholar
  32. 32.
    Siess W., Scherer B., Bohlig B., Roth P., Kurzmann I., Weber P.C. Platelet-membrane fatty acids, platelet aggregation, and thromboxane formation during a mackerel diet. Lancet 1:441–444 (1980).PubMedCrossRefGoogle Scholar
  33. 33.
    Leaf A., Weber P.C. Cardiovascular effects of n-3 fatty acids. N. Engl. J. Med. 318:549–557 (318).Google Scholar
  34. 34.
    Kromhout D., Bosschieter E.B., Coulander C. The inverse relation between fish consumption and 20-year mortality from coronary heart disease. N. Engl. J. Med. 312:1205–1216 (1985).PubMedCrossRefGoogle Scholar
  35. 35.
    Burr M.L., Gilbert J.F., Holiday R.M., Elwood P.C., Fehily A.M., Rogers S. Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART). Lancet 2:758–761 (1989).Google Scholar
  36. 36.
    Weiner B.H., Ockene I.S., Levine P.H., Guenoud H., Fisher M., Johnson B.F. Inhibition of atherosclerosis by cod-liver oil in a hyperlipidemic swine model. N. Engl. J. Med. 315-841-846 (1986).Google Scholar
  37. 37.
    Davis H.R., Bridenstine R.T., Vesselinovitch D., Wissler R.W. Fish oil inhibits development of atherosclerosis in Rhesus monkeys. Arteriosclerosis 7:441–449 (1987).PubMedCrossRefGoogle Scholar
  38. 38.
    Turpie A.G.G. Clinical studies: Evidence for intervention with specific antiplatelet drugs in arterial thromboembolism. Semin. Thromb. Hemostas. 14:4–49 (1988).Google Scholar
  39. 39.
    ISIS-2 collaborative group. Randomized trial of intravenous streptokinase, oral aspirin, both or neither among 17187 cases of suspected acute myocardial infarction: ISIS-2. Lancet II: 349 (1988).Google Scholar
  40. 40.
    The steering committee of the physicians health study research group. Preliminary report: findings from the aspirin component of the ongoing physicians health study. N. Engl. J. Med. 318:262-(1988).Google Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Wolfgang Siess
    • 1
  1. 1.Institut für Prophylaxe und Epidemiologie der KreislaufkrankheitenUniversität MünchenMünchen 2Federal Republic of Germany

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