Abstract
Background: Shear stress generated in stenosed arteries promotes platelet thrombi formation at the stenosed sites by accelerating the binding of von Willebrand factor (vWF) to platelets. Shear‐induced platelet aggregation (SIPA) has been studied in acute coronary syndromes, but not in chronic coronary disease.
Hypothesis: We investigated the effect of both the site and severity of coronary stenosis on SIPAin patients with chronic coronary artery disease.
Methods: Shear‐induced platelet aggregation was measured using platelet‐rich plasma in 49 patients (41 men and 8 women; mean age 61 ± 10 years) with coronary artery disease to evaluate the association between the extent of SIPA and coronary angiographic findings. Stenoses > 75% were considered severe. In all, 62 healthy individuals (54 men and 18 women; mean age 45 ± 7 years) served as controls. The correlation between SIPA and the site and severity of the coronary lesion, and parameters of coagulation and fibrinolysis were evaluated.
Results: Shear‐induced platelet aggregation was increased in the stenosis group (69.0 ± 10.6%) compared with the controls (57.7 ± 10.3%, p < 0.0001). Patients with severe stenosis in the proximal segments had significantly increased SIPA (p< 0.0001) and vWF larger multimer concentration (p < 0.0001) compared with the control group. A significant correlation existed between SIPA and the vWF larger multimer concentrationinall subjects studied (r= 0.422, p<0.0001).
Conclusions: Shear‐induced platelet aggregation is increased in patients with severe stenosis of the proximal coronary arteries and correlates with plasma concentrations of vWF larger multimers, suggesting that severe stenosis in the proximal segments is not only associated with an increased risk of significant my ocardial ischemia, but may also generate high shear stress in the stenosed artery and increase plasma vWF larger multimers, thereby promoting the formation of platelet thrombi.
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References
- 1. Fuster V, Badimon L, Badimon JJ, Chesebro JH: The pathogenesis of coronary artery disease and the acute coronary syndromes (I). N Engl J Med 1992; 326: 242–250 [DOI] [PubMed] [Google Scholar]
- 2. Fuster V, Badimon L, Badimon JJ, Chesebro JH: The pathogenesis of coronary artery disease and the acute coronary syndromes (II). N Engl J Med 1992; 326: 310–318 [DOI] [PubMed] [Google Scholar]
- 3. Davies MJ, Richardson PD, Woolf N, Katz DR, Mann J: Risk of thrombosis in human atherosclerotic plaques: Role of extracellular lipid, macrophage, and smooth muscle cell content. Br Heart J 1993; 69: 377–381 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4. Falk E, Shah PK, Fuster V: Coronary plaque disruption. Circulation 1995; 92: 657–671 [DOI] [PubMed] [Google Scholar]
- 5. Willerson JT: Conversion from chronic to acute coronary heart disease syndromes. Role of platelets and platelet products. Tex Heart Inst J 1995; 22: 13–19 [PMC free article] [PubMed] [Google Scholar]
- 6. Neumann FJ, Marx N, Gawaz M, Brand K, Ott I, Rokitta C, Sticherling C, Meinl C, May A, Schomig A: Induction of cytokine expression in leukocytes by binding of thrombin‐stimulated platelets. Circulation 1997; 95: 2387–2394 [DOI] [PubMed] [Google Scholar]
- 7. Holme PA, Orvim U, Hamers MJAG, Solum NO, Brosstad FR, Barstad RM, Sakariassen KS: Shear‐induced platelet activation and platelet microparticle formation at blood flow conditions as in arteries with a severe stenosis. Arterioscl Thromb Vasc Biol 1997; 17: 646–653 [DOI] [PubMed] [Google Scholar]
- 8. Gibson MC, Diaz L, Kandarpa K, Sacks FM, Paternak RC, Sandor T, Feldman C, Stone PH: Relation of vessel wall shear stress to atherosclerosis progression in human coronary arteries. Arterioscl Thromb 1993; 13: 310–315 [DOI] [PubMed] [Google Scholar]
- 9. Folts J: An in vivo model of experimental arterial stenosis, intimal damage, and periodic thrombosis. Circulation 1991; 83 (suppl IV): IV3–14 [PubMed] [Google Scholar]
- 10. Taeymans Y, Théroux P, Lesperance J, Waters D: Quantitative angiographic morphology of the coronary artery lesions at risk of thrombotic occlusion. Circulation 1992; 85: 78–85 [DOI] [PubMed] [Google Scholar]
- 11. Kapiotis S, Jilma B, Quenhenberger P, Ruzicka K, Handler S, Speiser W: Morning hypercoagulability and hypofibrinolysis: Diurnal variations in circulating activated factor VII, prothrombin fragment F1 + 2, and plasin‐plasmin inhibitor complex. Circulation 1997; 96: 19–21 [DOI] [PubMed] [Google Scholar]
- 12. Patrono C, Renda G: Platelet activation and inhibition in unstable coronary syndromes. Am J Cardiol 1997; 80: 17E–20E [DOI] [PubMed] [Google Scholar]
- 13. Ghaisas NK, Shahi CN, Foley B, Goggins M, Crean P, Kelly A, Kelleher D, Walsh M: Elevated levels of circulating soluble adhesion molecules in peripheral blood of patients with unstable angina. Am J Cardiol 1997; 80: 617–619 [DOI] [PubMed] [Google Scholar]
- 14. Moreno PR, Bernardi VH, Lopez‐Cuellar J, Murcia AM, Palacios IF, Gold HK, Mehran R, Sharma SK, Nemerson Y, Fuster V, Fallon JT: Macrophages, smooth muscle cells, and tissue factor in unstable angina. Implications for cell‐mediated thrombogenicity in acute coronary syndromes. Circulation 1996; 94: 3090–3097 [DOI] [PubMed] [Google Scholar]
- 15. Fuster V, Badimon L, Cohen M, Ambrose JA, Badimon JJ, Chesebro J: Insights into the pathogenesis of acute ischemic syndromes. Circulation 1988; 77: 1213–1220 [DOI] [PubMed] [Google Scholar]
- 16. Ikeda Y, Handa M, Kawano K, Kamata T, Murata M, Araki Y, Anbo H, Kawai Y, Watanabe K, Itagaki I, Sakai K, Ruggeri ZM: The role of von Willebrand factor and fibrinogen in platelet aggregation under varying shear stress. J Clin Invest 1991; 87: 1234–1240 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17. Uchiyama S, Yamazaki M, Maruyama S, Handa M, Ikeda Y, Fukuyama M, Itagaki I: Shear‐induced platelet aggregation in cerebral ischemia. Stroke 1994; 25: 1547–1551 [DOI] [PubMed] [Google Scholar]
- 18. Ikeda Y, Handa M, Kamata T, Kawano K, Kawai Y, Watanabe K, Kawakami K, Sakai K, Fukuyama M, Itagaki I, Yoshioka A, Ruggeri ZM: Transmembrane calcium influx associated with von Willebrand factor binding to GPIb in the initiation of shear‐induced platelet aggregation. Thromb Haemost 1993; 69: 496–502 [PubMed] [Google Scholar]
- 19. The Principal Investigators of CASS and Associates : The National Heart, Lung, and Blood Institute Coronary Artery Surgery Study (CASS). Circulation 1981; 63 (suppl I): I‐1–8 [Google Scholar]
- 20. AHA Committee Report : A reporting system on patients evaluated for coronary artery disease. Report of the Ad Hoc Committee for grading of coronary artery disease, Council on Cardiovascular Surgery, American Heart Association. News from the American Heart Association. Circulation 1975; 51: 5–40 [DOI] [PubMed] [Google Scholar]
- 21. Davies MJ, Thomas AC: Plaque fissuring: The cause of acute myocardial infarction, sudden ischemic death, and crescendo angina. Br Heart J 1985; 53: 363–373 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22. Fuster V, Stein B, Ambrose JA, Badimon L, Badimon JJ, Chesebro JH: Atherosclerotic plaque rapture and thrombosis. Evolving concepts. Circulation 1990; 82 (suppl II): II‐47–59 [PubMed] [Google Scholar]
- 23. Goto S, Sakai H, Goto M, Ono M, Ikeda Y, Handa S, Ruggeri ZM: Enhanced shear‐induced platelet aggregation in acute myocardial infarction. Circulation 1999; 99: 608–613 [DOI] [PubMed] [Google Scholar]
- 24. Tokuue J, Hayashi J, Hata Y, Nakahara K, Ikeda Y: Enhanced platelet aggregability under high shear stress after treadmill exercise in patients with effort angina. Thromb Haemost 1996; 75: 833–837 [PubMed] [Google Scholar]
- 25. Goldsmith HL, Turitto VT: Rheological aspects of thrombosis and haemostasis: Basic principles and applications. Thromb Haemost 1986; 55: 415–435 [PubMed] [Google Scholar]
- 26. Thompson SG, Kienast J, Pyke SDM, Haverkate F, van de Loo JCW: Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. N Engl J Med 1995; 332: 635–641 [DOI] [PubMed] [Google Scholar]
- 27. Strony J, Phillips M, Brands D, Moake J, Adelman B: Aurintri‐carboxylic acid in a canine model of coronary artery thrombosis. Circulation 1990; 81: 1106–1114 [DOI] [PubMed] [Google Scholar]
- 28. Badimon L, Badimon J, Chesebro H, Fuster V: Inhibition of thrombus formation: Blockade of adhesive glycoprotein mechanisms versus blockade of the cyclooxygenase pathway (abstr). J Am Coll Cardiol 1988; 11: 30A [Google Scholar]
- 29. Yao S, Ober JC, Garfinkel LI, Hagay Y, Ezov N, Ferguson J, Anderson HV, Panet A, Gorecki M, Buja LM, Willerson JT: Blockade of platelet membrane glycoprotein Ib receptors delays intracoro‐nary thrombogenesis, enhances thrombolysis, and delays coronary artery reocclusion in dogs. Circulation 1994; 89: 2822–2828 [DOI] [PubMed] [Google Scholar]
- 30. Okada M, Murata M, Suzuki H, Kitaguchi T, Handa M, Watanabe K, Sakai K, Tanoue K, Ikeda Y: Von Willebrand factor binding to glycoprotein Ib/IX induces platelet shape change under high shear stress conditions—an electron microscopic study. Thromb Haemost 1997; 78: (suppl): 644 [Google Scholar]
- 31. Moake JL, Turner NA, Stathopoulos NA, Nolasco LN, Hellums JD: Involvement of large plasma von Willebrand factor (vWF) mul‐timers and unusually large vWF forms derived from endothelial cells in shear stress‐induced platelet aggregation. J Clin Invest 1986; 78: 1456–1461 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32. Siedlecki CA, Lestini BJ, Kottke‐Marchant K, Eppel SJ, Wilson DL, Marchant RE: Shear‐dependent changes in the three‐dimensional structure of human von Willebrand factor. Blood 1996; 88: 2939–2950 [PubMed] [Google Scholar]
- 33. Goto S, Ikeda Y, Murata M, Handa M, Takahashi E, Yoshioka A, Fujimura Y, Fukuyama M, Handa S, Ogawa S: Epinephrine augments von Willebrand factor‐dependent shear‐induced platelet aggregation. Circulation 1992; 86: 1859–1863 [DOI] [PubMed] [Google Scholar]
- 34. Savage B, Saldivar E, Ruggeri ZM: Initiation of platelet adhesion by arrest onto fibrinogen or translocation on von Willebrand factor. Cell 1996; 84: 289–297 [DOI] [PubMed] [Google Scholar]