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Specific Platelet Mediators and the Abrupt Progression of Coronary Artery Stenoses

Experimental Evidence and Potential Clinical Implications
  • James T. Willerson
  • Paolo Golino
  • L. Maximilian Buja

Abstract

Acute coronary heart disease syndromes, including unstable angina and acute myocardial infarction, are usually caused by a primary decrease in coronary blood flow and myocardial oxygen delivery.1–15 Unstable angina occurs in patients with endothelial injury or ulceration at the site of an atherosclerotic plaque and some patients have an intraluminal coronary artery thrombosis.4–6,9–11 Falk7 and Davies and Thomas8 have shown that atherosclerotic plaque Assuring or rupture may lead to coronary arterial thrombosis and the development of unstable angina, acute myocardial infarction, or sudden death. Patients with Q-wave myocardial infarcts often have ulcerated or atherosclerotic plaques and the subsequent development of occlusive coronary artery thrombi.2,3 Patients with non-Q-wave infarcts (usually subendocardial infarcts) much less commonly have coronary artery thrombi that are permanently occlusive, but instead these patients have transient reductions in coronary blood flow followed by reperfusion and sometimes partially occlusive thrombi.3,16 We believe that transient reductions in coronary blood flow are most likely related to intermittent platelet aggregation and vasoconstriction contributed to by the release of selected mediators from aggregating platelets at sites of coronary artery endothelial injury and stenosis.4,5,17

Keywords

Platelet Aggregation Leave Anterior Descend Unstable Angina Coronary Blood Flow Coronary Artery Stenosis 
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.

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References

  1. 1.
    Maseri, A., Pesola, A., Marzilli, M., Seven, S., Parodi, O., L’Abbate, A., Ballestra, A. M., Maltinti, G., DeNes, D. M., and Biagini, A., 1977, Coronary vasospasm in angina pectoris, Lancet 1:713–717.PubMedCrossRefGoogle Scholar
  2. 2.
    DeWood, M. A., Spores, J., Notske, R., Mouser, L. T., Burroughs, R., Golden, M. S., and Lang, H. T., 1980, Prevalence of total coronary occlusion during the early hours of transmural myocardial infarction, N. Engl. J. Med. 303:897–902.PubMedCrossRefGoogle Scholar
  3. 3.
    Buja, L. M., and Willerson, J. T., 1981, Clinicopathologic correlates of acute ischemic heart disease syndromes, Am. J. Cardiol. 47:343–356.PubMedCrossRefGoogle Scholar
  4. 4.
    Willerson, J. T., Campbell, W. B., Winniford, M. D., Schmitz, J., Apprill, P., Firth, B. G., Ashton, J., Smitherman, T., Bush, L., and Buja, L. M., 1984, Conversion from chronic to acute coronary artery disease: Speculation regarding mechanisms, Am. J. Cardiol. 54:1349–1354.PubMedCrossRefGoogle Scholar
  5. 5.
    Willerson, J. T., Hillis, L. D., Winniford, M. D., and Buja, L. M., 1986, Speculations regarding mechanisms responsible for acute ischemic heart disease syndromes, J. Am. Coll. Cardiol. 8:245–250.PubMedCrossRefGoogle Scholar
  6. 6.
    Sherman, C. J., Litvak, F., Grundfest, W., Lee, M., Hickey, A., Chaux, A., Kass, R., Blanche, C., Matloff, J., and Morgenstern, L., 1986, Coronary angioscopy in patients with unstable angina pectoris, N. Engl. J. Med. 315:913–919.PubMedCrossRefGoogle Scholar
  7. 7.
    Falk, E., 1983, Plaque rupture with severe pre-existing stenosis precipitating coronary thrombosis: Characteristics of coronary atherosclerotic plaques, Br. Heart J. 50:127–134.PubMedCrossRefGoogle Scholar
  8. 8.
    Davies, M. J., and Thomas, A. C., 1985, Plaque Assuring—The cause of acute myocardial infarction, sudden ischemic death, and crescendo angina, Br. Heart J. 53:363–373.PubMedCrossRefGoogle Scholar
  9. 9.
    Gotoh, K., Minamino, T., Katoh, O., Hamano, Y., Fukui, S., Hori, M., Kusuoka, H., Mishima, M., Inoue, M., and Kamada, T., 1988, The role of intracoronary thrombus in unstable angina: Angiographic assessment and thrombolytic therapy during ongoing anginal attacks, Circulation 77:526–534.PubMedCrossRefGoogle Scholar
  10. 10.
    Hirsh, P. D., Hillis, L. D., Campbell, W. B., Firth, B. G., and Willerson, J. T., 1981, Release of prostaglandins and thromboxane into the coronary circulation in patients with ischemic heart disease, N. Engl. J. Med. 304: 685–691.PubMedCrossRefGoogle Scholar
  11. 11.
    Fitzgerald, D. J., Roy, L., Catella, F., and Fitzgerald, G. A., 1986, Platelet activation in unstable coronary disease, N. Engl. J. Med. 315:983–989.PubMedCrossRefGoogle Scholar
  12. 12.
    Hamm, C. W., Lorenz, R., Bleifeld, W., Kupper, W., Wober, W., and Weber, P. C., 1987, Biochemical evidence of platelet activation in patients with persistent unstable angina, J. Am. Coll. Cardiol. 9:998–1004.CrossRefGoogle Scholar
  13. 13.
    Van den Berg, E. K., Schmitz, J. M., Benedict, C. R., Malloy, C. R., Willerson, J. T., and Dehmer, G. J., 1989, Transcardiac serotonin concentration is increased in selected patients with limiting angina and complex coronary lesion morphology, Circulation 79:116–124.PubMedCrossRefGoogle Scholar
  14. 14.
    Rubany, G. M., Frye, R. L., Holmes, D. R., and Vanhoutte, P.M., 1987, Vasoconstrictor activity of coronary sinus plasma from patients with coronary artery disease, J. Am. Coll. Cardiol. 9:1243–1249.CrossRefGoogle Scholar
  15. 15.
    Ambrose, J. A., Winters, S. L., Arora, R. R., Eng, A., Riccio, A., Gorlin, R., and Fuster, V., 1986, Angiographic evolution of coronary artery morphology in unstable angina, J. Am. Coll. Cardiol. 7:472–478.PubMedCrossRefGoogle Scholar
  16. 16.
    Gibson, R. S., Beller, G. A., Gheorghiade, M., Nygaard, T. W., Watson, D. D., Huey, B. L., Sayre, S. L., and Kaiser, D. L., 1986, The prevalence and clinical significance of residual myocardial ischemia 2 weeks after uncomplicated non-Q wave infarction: A prospective natural history study, Circulation 73:1186–1198.PubMedCrossRefGoogle Scholar
  17. 17.
    Willerson, J. T., Golino, P., Eidt, J., Campbell, W.B., and Buja, L. M., 1989, Specific platelet mediators and unstable coronary artery lesions: Experimental evidence and potential clinical implications, Circulation 80: 198–205.PubMedCrossRefGoogle Scholar
  18. 18.
    Folts, J. D., Crowell, E. B., Jr., and Rowe, C. G., 1976, Platelet aggregation in partially obstructed vessels and its elimination by aspirin, Circulation 54:365–370.PubMedCrossRefGoogle Scholar
  19. 19.
    Bush, L. R., Campbell, W. B., Tilton, G. D., Buja, L. M., and Willerson, J. T., 1984, Effects of the selective thromboxane synthetase inhibitor, dazoxiben, on variations in cyclic blood flow in stenosed canine coronary arteries, Circulation 69:1161–1170.PubMedCrossRefGoogle Scholar
  20. 20.
    Ashton, J. H., Schmitz, J. M., Campbell, W. B., Ogletree, M. L., Raheja, S., Taylor, A. L., Fitzgerald, C., Buja, L. M., and Willerson, J. J., 1986, Inhibition of cyclic flow variations in stenosed canine coronary arteries by thromboxane A2/prostaglandin H2 receptor antagonists, Circ. Res. 59:568–578.PubMedCrossRefGoogle Scholar
  21. 21.
    Schmitz, J., Apprill, P., Buja, L. M., Willerson, J. J., and Campbell, W. B., 1985, Vascular prostaglandin and thromboxane production in a canine model of myocardial ischemia, Circ. Res. 57:223–231.PubMedCrossRefGoogle Scholar
  22. 22.
    Golino, P., Ashton, J. H., Buja, L. M., Rosolowsky, M., Taylor, A. L., McNatt, J., Campbell, W. B., and Willerson, J. J., 1989, Local platelet activation causes vasoconstriction of large epicardial canine coronary arteries in vivo: Thromboxane A2 and serotonin are possible mediators, Circulation 79:154–166.PubMedCrossRefGoogle Scholar
  23. 23.
    Golino, P., Buja, L. M., Ashton, J. H., Kulkarni, P., Taylor, A., and Willerson, J. T., 1988, Effect of thromboxane and serotonin receptor antagonists on intracoronary platelet deposition in dogs with experimentally stenosed coronary arteries, Circulation 78:701–711.PubMedCrossRefGoogle Scholar
  24. 24.
    Ashton, J. H., Benedict, C. R., Fitzgerald, C., Raheja, S., Taylor, A., Campbell, W. B., Buja, L. M., and Willerson, J. T., 1986, Serotonin is a mediator of cyclic flow variations in stenosed canine coronary arteries, Circulation 73:572–578.PubMedCrossRefGoogle Scholar
  25. 25.
    Bush, L. R., Campbell, W. B., Kern, K., Tilton, G. D., Apprill, P., Ashton, J., Schmitz, J., Buja, L. M., and Willerson, J. J., 1984, Xhe effects of alpha2-adrenergic and serotonergic receptor antagonists on cyclic blood flow alterations in stenosed canine coronary arteries, Circ. Res. 55:642–652.PubMedCrossRefGoogle Scholar
  26. 26.
    Ashton, J. H., Ogletree, M. L., Michel, I. M., Golino, P., McNatt, J. M., Taylor, A. L., Raheja, S., Schmitz, J., Buja, L. M., Campbell, W. B., and Willerson, J. J., 1987, Cooperative mediation by serotonin S2 and thromboxane A2/prostaglandin H2 receptor activation of cyclic flow variations in dogs with severe coronary artery stenoses, Circulation 76:952–959.PubMedCrossRefGoogle Scholar
  27. 27.
    Ashton, J. H., Golino, P., McNatt, J. M., Buja, L. M., and Willerson, J. T., 1989, Serotonin S2 receptor blockade (LY53857) combined with thromboxane A2/prostaglandin H2 receptor blockade (SQ29,548) provide protection against epinephrine-induced intermittent thrombosis in severely narrowed canine coronary arteries, J. Am. Coll. Cardiol. 13:755–763.PubMedCrossRefGoogle Scholar
  28. 28.
    Eidt, J. F., Ashton, J., Golino, P., McNatt, J., Buja, L. M., and Willerson, J. T., 1989, Thromboxane A2 and serotonin mediate coronary blood flow reductions in unsedated dogs, Am. J. Physiol. 26:H873–H882.Google Scholar
  29. 29.
    Eidt, J. F., Ashton, J., McNatt, J., Buja, L. M., and Willerson, J. T., 1989, Treadmill exercise promotes cyclical alterations in coronary blood flow in dogs with coronary artery stenosis and endothelial injury, J. Clin. Invest. 84:517–527.PubMedCrossRefGoogle Scholar
  30. 30.
    Fishman, J. A., Ryan, G. B., and Karnovsky, M. J., 1975, Endothelial regeneration in the rat carotid artery and the significance of endothelial denudation in the pathogenesis of myointimal thickening, Lab. Invest. 32: 339–351.PubMedGoogle Scholar
  31. 31.
    Austin, G. E., Ratliff, N. G., Hollman, J., Tabei, S., and Phillips, D. F., 1985, Intimai proliferation of smooth muscle cells as an explanation for recurrent coronary artery stenosis after percutaneous transluminal coronary angioplasty, J. Am. Coll. Cardiol. 6:369–375.PubMedCrossRefGoogle Scholar
  32. 32.
    Itoh, Y., Yanagisawa, M., Ohkubo, S., Kimura, C., Kosaka, T., Inoue, A., Ishida, N., Mitsui, Y., Onda, H., and Fujino, M., 1988, Cloning and sequence analysis of cDNA encoding the precursor of a human endothelium-derived vasoconstrictor peptide, endothelin: Identity of human and porcine endothelin, FEBS Lett. 231:440–444.PubMedCrossRefGoogle Scholar
  33. 33.
    Jonasson, L., Holm, J., and Hansson, G. K., 1988, Cyclosporin A inhibits smooth muscle proliferation in the vascular response to injury, Proc. Natl. Acad. Sci. USA 85:2302–2306.CrossRefGoogle Scholar
  34. 34.
    Berk, B.C., Alexander, R. W., Brock, T. A., Gimbrone, M. A., Jr., and Webb, R. C., 1986, Vasoconstriction: A new activity for platelet-derived growth factor, Science 232:87.PubMedCrossRefGoogle Scholar
  35. 35.
    Waterfield, M. D., Scrace, G. T., Whittle, N., Stroobant, P., Johnsson, A., Wasteson, A., Westermark, B., Heldin, C. H., Huang, J. S., and Deuel, T. F., 1983, Platelet-derived growth factor is structurally related to the putative transforming protein p28cis of simian sarcoma virus, Nature 304:35–39.PubMedCrossRefGoogle Scholar
  36. 36.
    Williams, L. T., Tremble, P. M., Lavin, M. R., and Sunday, M. E., 1984, Platelet-derived growth factor receptors form a high affinity state in membrane preparations: Kinetics and affinity cross-linking studies, J. Biol. Chem. 259:5287–5294.PubMedGoogle Scholar
  37. 37.
    Roberts, A. B., Sporn, M. B., Assoian, R. K., Smith, J. M., Roche, N. S., Wakefield, L. M., Heine, U. I., Liotta, L. A., Falanga, V., and Kehrl, J. H., 1986, Transforming growth factor type beta: Rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro, Proc. Natl. Acad. Sci. USA 83:4167–4171.PubMedCrossRefGoogle Scholar
  38. 38.
    Akhurst, R. J., Fee, F., and Balmain, A., 1988, Localized production of TGF-beta mRNA in tumour promoter-stimulated mouse epidermis, Nature 331:363–364.PubMedCrossRefGoogle Scholar
  39. 39.
    Lewis, H. D., Jr., Davis, J. W., Archibald, D. G., Steinke, W. E., Smitherman, T. C., Doherty, J. E., III., Schnaper, H. W., LeWinter, M. M., Linares, E., Pouget, J. M., Sabharwal, S. C., Chesler, E., and DeMots, H., 1983, Protective effects of aspirin against acute myocardial infarction and death in men with unstable angina, N. Engl. J. Med. 309:396–403.PubMedCrossRefGoogle Scholar
  40. 40.
    Cairns, J. A., Gent, M., Singer, J., Finnie, K. J., Froggatt, G. M., Holder, D. A., Jablonsky, G., Kostuk, W. J., Melendez, L. J., and Myers, M. G., 1985, Aspirin, sulfinpyrazone, or both in unstable angina, N. Engl. J. Med. 313:1369–1375.PubMedCrossRefGoogle Scholar
  41. 41.
    Hirsh, P. D., Campbell, W. B., Willerson, J. T., and Hillis, L. D., 1981, Prostaglandins and ischemic heart disease, Am. J. Med. 71:1009–1026.PubMedCrossRefGoogle Scholar
  42. 42.
    Ludmer, P. L., Selwyn, A. P., Shook, T. L., Wayne, R. R., Mudge, G. H., Alexander, R. W., and Ganz, P., 1986, Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries, N. Engl. J. Med. 315:1046–1051.PubMedCrossRefGoogle Scholar
  43. 43.
    Nabel, E. G., Ganz, P., Gordon, J. B., Alexander, R. W., and Selwyn, A. P., 1988, Dilation of normal and constriction of atherosclerotic coronary arteries caused by the cold pressor test, Circulation 77:43–52.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1992

Authors and Affiliations

  • James T. Willerson
    • 1
    • 2
  • Paolo Golino
    • 3
  • L. Maximilian Buja
    • 1
    • 4
  1. 1.Department of Internal MedicineUniversity of Texas Medical SchoolHoustonUSA
  2. 2.Cardiology ResearchTexas Heart InstituteHoustonUSA
  3. 3.Division of CardiologyUniversity of Naples II School of MedicineNaplesItaly
  4. 4.Department of PathologyUniversity of Texas Medical SchoolHoustonUSA

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