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. 1995;22(1):13–19.

Conversion from chronic to acute coronary heart disease syndromes. Role of platelets and platelet products.

J T Willerson 1
PMCID: PMC325205  PMID: 7787465

Abstract

Vascular endothelial injury associated with arterial narrowing leads to platelet adhesion and aggregation at the site of endothelial injury and to the local accumulation of several mediators that promote platelet aggregation and vasoconstriction, including thromboxane A2, serotonin, adenosine diphosphate, platelet activating factor, oxygen-derived free radicals, activated thrombin, and tissue factor. At the same sites of endothelial injury, there is a reduction in absolute or relative amounts of the endogenous inhibitors of platelet aggregation and vasoconstriction, including prostacyclin, endothelium-derived relaxing factor (nitric oxide), and tissue plasminogen activator; the loss of the effects of the endogenous inhibitors preventing platelet aggregation and vasoconstriction helps to create a prothrombotic and vasoconstrictive environment. Endothelial injury occurs as a result of atherosclerotic plaque fissuring or ulceration, flow shear stress, hypertension, diabetes mellitus, immune complex deposition, infection, and mechanical injury in the form of diagnostic and therapeutic catheterization. Endothelial injury and the accumulation of platelet- and other cell-derived mediators promotes neointimal proliferation in an exaggerated wound-healing response, resulting in further anatomic narrowing of artery in the subsequent days and weeks. Future methods that may prove useful in protecting the individual with these vascular problems from acute myocardial infarction and its consequences are inhibition of multiple mediators of platelet aggregation and vasoconstriction, restoration of the presence of the normal endogenous inhibitors of platelet aggregation and vasoconstriction, and/or rapid therapeutic regeneration of the injured endothelium.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Apprill P., Schmitz J. M., Campbell W. B., Tilton G., Ashton J., Raheja S., Buja L. M., Willerson J. T. Cyclic blood flow variations induced by platelet-activating factor in stenosed canine coronary arteries despite inhibition of thromboxane synthetase, serotonin receptors, and alpha-adrenergic receptors. Circulation. 1985 Aug;72(2):397–405. doi: 10.1161/01.cir.72.2.397. [DOI] [PubMed] [Google Scholar]
  2. Ashton J. H., Golino P., McNatt J. M., Buja L. M., Willerson J. T. Serotonin S2 and thromboxane A2-prostaglandin H2 receptor blockade provide protection against epinephrine-induced cyclic flow variations in severely narrowed canine coronary arteries. J Am Coll Cardiol. 1989 Mar 1;13(3):755–763. doi: 10.1016/0735-1097(89)90622-0. [DOI] [PubMed] [Google Scholar]
  3. 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. Cooperative mediation by serotonin S2 and thromboxane A2/prostaglandin H2 receptor activation of cyclic flow variations in dogs with severe coronary artery stenoses. Circulation. 1987 Oct;76(4):952–959. doi: 10.1161/01.cir.76.4.952. [DOI] [PubMed] [Google Scholar]
  4. Ashton J. H., Schmitz J. M., Campbell W. B., Ogletree M. L., Raheja S., Taylor A. L., Fitzgerald C., Buja L. M., Willerson J. T. Inhibition of cyclic flow variations in stenosed canine coronary arteries by thromboxane A2/prostaglandin H2 receptor antagonists. Circ Res. 1986 Nov;59(5):568–578. doi: 10.1161/01.res.59.5.568. [DOI] [PubMed] [Google Scholar]
  5. Bush L. R., Campbell W. B., Buja L. M., Tilton G. D., Willerson J. T. Effects of the selective thromboxane synthetase inhibitor dazoxiben on variations in cyclic blood flow in stenosed canine coronary arteries. Circulation. 1984 Jun;69(6):1161–1170. doi: 10.1161/01.cir.69.6.1161. [DOI] [PubMed] [Google Scholar]
  6. Bush L. R., Campbell W. B., Tilton G. D., Buja L. M., Willerson J. T. Effects of the selective thromboxane synthetase inhibitor, dazoxiben, on cyclic flow variations in stenosed canine coronary arteries. Trans Assoc Am Physicians. 1983;96:103–112. [PubMed] [Google Scholar]
  7. Davies M. J., Thomas A. C. Plaque fissuring--the cause of acute myocardial infarction, sudden ischaemic death, and crescendo angina. Br Heart J. 1985 Apr;53(4):363–373. doi: 10.1136/hrt.53.4.363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Drake T. A., Morrissey J. H., Edgington T. S. Selective cellular expression of tissue factor in human tissues. Implications for disorders of hemostasis and thrombosis. Am J Pathol. 1989 May;134(5):1087–1097. [PMC free article] [PubMed] [Google Scholar]
  9. Eidt J. F., Allison P., Noble S., Ashton J., Golino P., McNatt J., Buja L. M., Willerson J. T. Thrombin is an important mediator of platelet aggregation in stenosed canine coronary arteries with endothelial injury. J Clin Invest. 1989 Jul;84(1):18–27. doi: 10.1172/JCI114138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Eidt J. F., Ashton J., Golino P., McNatt J., Buja L. M., Willerson J. T. Thromboxane A2 and serotonin mediate coronary blood flow reductions in unsedated dogs. Am J Physiol. 1989 Sep;257(3 Pt 2):H873–H882. doi: 10.1152/ajpheart.1989.257.3.H873. [DOI] [PubMed] [Google Scholar]
  11. Falk E. Unstable angina with fatal outcome: dynamic coronary thrombosis leading to infarction and/or sudden death. Autopsy evidence of recurrent mural thrombosis with peripheral embolization culminating in total vascular occlusion. Circulation. 1985 Apr;71(4):699–708. doi: 10.1161/01.cir.71.4.699. [DOI] [PubMed] [Google Scholar]
  12. Folts J. D., Crowell E. B., Jr, Rowe G. G. Platelet aggregation in partially obstructed vessels and its elimination with aspirin. Circulation. 1976 Sep;54(3):365–370. doi: 10.1161/01.cir.54.3.365. [DOI] [PubMed] [Google Scholar]
  13. Fuster V., Badimon L., Cohen M., Ambrose J. A., Badimon J. J., Chesebro J. Insights into the pathogenesis of acute ischemic syndromes. Circulation. 1988 Jun;77(6):1213–1220. doi: 10.1161/01.cir.77.6.1213. [DOI] [PubMed] [Google Scholar]
  14. Fuster V. Lewis A. Conner Memorial Lecture. Mechanisms leading to myocardial infarction: insights from studies of vascular biology. Circulation. 1994 Oct;90(4):2126–2146. doi: 10.1161/01.cir.90.4.2126. [DOI] [PubMed] [Google Scholar]
  15. Golino P., Ambrosio G., Ragni M., Pascucci I., Triggiani M., Oriente A., McNatt J., Buja L. M., Condorelli M., Chiariello M. Short-term and long-term role of platelet activating factor as a mediator of in vivo platelet aggregation. Circulation. 1993 Sep;88(3):1205–1214. doi: 10.1161/01.cir.88.3.1205. [DOI] [PubMed] [Google Scholar]
  16. Golino P., Ashton J. H., Buja L. M., Rosolowsky M., Taylor A. L., McNatt J., Campbell W. B., Willerson J. T. Local platelet activation causes vasoconstriction of large epicardial canine coronary arteries in vivo. Thromboxane A2 and serotonin are possible mediators. Circulation. 1989 Jan;79(1):154–166. doi: 10.1161/01.cir.79.1.154. [DOI] [PubMed] [Google Scholar]
  17. Hirsh P. D., Hillis L. D., Campbell W. B., Firth B. G., Willerson J. T. Release of prostaglandins and thromboxane into the coronary circulation in patients with ischemic heart disease. N Engl J Med. 1981 Mar 19;304(12):685–691. doi: 10.1056/NEJM198103193041201. [DOI] [PubMed] [Google Scholar]
  18. Kleiman N. S., Ohman E. M., Califf R. M., George B. S., Kereiakes D., Aguirre F. V., Weisman H., Schaible T., Topol E. J. Profound inhibition of platelet aggregation with monoclonal antibody 7E3 Fab after thrombolytic therapy. Results of the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) 8 Pilot Study. J Am Coll Cardiol. 1993 Aug;22(2):381–389. doi: 10.1016/0735-1097(93)90041-x. [DOI] [PubMed] [Google Scholar]
  19. Pakala R., Willerson J. T., Benedict C. R. Mitogenic effect of serotonin on vascular endothelial cells. Circulation. 1994 Oct;90(4):1919–1926. doi: 10.1161/01.cir.90.4.1919. [DOI] [PubMed] [Google Scholar]
  20. Schmitz J. M., Apprill P. G., Buja L. M., Willerson J. T., Campbell W. B. Vascular prostaglandin and thromboxane production in a canine model of myocardial ischemia. Circ Res. 1985 Aug;57(2):223–231. doi: 10.1161/01.res.57.2.223. [DOI] [PubMed] [Google Scholar]
  21. Simoons M. L., de Boer M. J., van den Brand M. J., van Miltenburg A. J., Hoorntje J. C., Heyndrickx G. R., van der Wieken L. R., de Bono D., Rutsch W., Schaible T. F. Randomized trial of a GPIIb/IIIa platelet receptor blocker in refractory unstable angina. European Cooperative Study Group. Circulation. 1994 Feb;89(2):596–603. doi: 10.1161/01.cir.89.2.596. [DOI] [PubMed] [Google Scholar]
  22. Topol E. J., Califf R. M., Weisman H. F., Ellis S. G., Tcheng J. E., Worley S., Ivanhoe R., George B. S., Fintel D., Weston M. Randomised trial of coronary intervention with antibody against platelet IIb/IIIa integrin for reduction of clinical restenosis: results at six months. The EPIC Investigators. Lancet. 1994 Apr 9;343(8902):881–886. doi: 10.1016/s0140-6736(94)90007-8. [DOI] [PubMed] [Google Scholar]
  23. Willerson J. T., Campbell W. B., Winniford M. D., Schmitz J., Apprill P., Firth B. G., Ashton J., Smitherman T., Bush L., Buja L. M. Conversion from chronic to acute coronary artery disease: speculation regarding mechanisms. Am J Cardiol. 1984 Dec 1;54(10):1349–1354. doi: 10.1016/s0002-9149(84)80095-8. [DOI] [PubMed] [Google Scholar]
  24. Willerson J. T., Golino P., Eidt J., Campbell W. B., Buja L. M. Specific platelet mediators and unstable coronary artery lesions. Experimental evidence and potential clinical implications. Circulation. 1989 Jul;80(1):198–205. doi: 10.1161/01.cir.80.1.198. [DOI] [PubMed] [Google Scholar]
  25. Willerson J. T., Yao S. K., McNatt J., Benedict C. R., Anderson H. V., Golino P., Murphree S. S., Buja L. M. Frequency and severity of cyclic flow alternations and platelet aggregation predict the severity of neointimal proliferation following experimental coronary stenosis and endothelial injury. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10624–10628. doi: 10.1073/pnas.88.23.10624. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Yao S. K., McNatt J., Cui K., Anderson H. V., Maffrand J. P., Buja L. M., Willerson J. T. Combined ADP and thromboxane A2 antagonism prevents cyclic flow variations in stenosed and endothelium-injured arteries in nonhuman primates. Circulation. 1993 Dec;88(6):2888–2893. doi: 10.1161/01.cir.88.6.2888. [DOI] [PubMed] [Google Scholar]
  27. Yao S. K., Ober J. C., Ferguson J. J., Maffrand J. P., Anderson H. V., Buja L. M., Willerson J. T. Clopidogrel is more effective than aspirin in preventing coronary artery reocclusion after thrombolysis. Trans Assoc Am Physicians. 1993;106:110–119. [PubMed] [Google Scholar]
  28. Yao S. K., Ober J. C., Gonenne A., Clubb F. J., Jr, Krishnaswami A., Ferguson J. J., Anderson H. V., Gorecki M., Buja L. M., Willerson J. T. Active oxygen species play a role in mediating platelet aggregation and cyclic flow variations in severely stenosed and endothelium-injured coronary arteries. Circ Res. 1993 Nov;73(5):952–967. doi: 10.1161/01.res.73.5.952. [DOI] [PubMed] [Google Scholar]
  29. Yao S. K., Ober J. C., Krishnaswami A., Ferguson J. J., Anderson H. V., Golino P., Buja L. M., Willerson J. T. Endogenous nitric oxide protects against platelet aggregation and cyclic flow variations in stenosed and endothelium-injured arteries. Circulation. 1992 Oct;86(4):1302–1309. doi: 10.1161/01.cir.86.4.1302. [DOI] [PubMed] [Google Scholar]
  30. Yao S. K., Ober J. C., McNatt J., Benedict C. R., Rosolowsky M., Anderson H. V., Cui K., Maffrand J. P., Campbell W. B., Buja L. M. ADP plays an important role in mediating platelet aggregation and cyclic flow variations in vivo in stenosed and endothelium-injured canine coronary arteries. Circ Res. 1992 Jan;70(1):39–48. doi: 10.1161/01.res.70.1.39. [DOI] [PubMed] [Google Scholar]
  31. van den Berg E. K., Schmitz J. M., Benedict C. R., Malloy C. R., Willerson J. T., Dehmer G. J. Transcardiac serotonin concentration is increased in selected patients with limiting angina and complex coronary lesion morphology. Circulation. 1989 Jan;79(1):116–124. doi: 10.1161/01.cir.79.1.116. [DOI] [PubMed] [Google Scholar]

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