Abstract
Vigorous exercise transiently enhances the risk of primary cardiac arrest. Shear-induced platelet aggregation (SIPA) is an important mechanism in arterial thrombogenesis. This study investigates whether intense exercise affects SIPA, and elucidates mechanisms that underlie SIPA. Eighteen sedentary healthy men engaged in intense exercise (about 80% of maximal oxygen consumption) for 40 min on a bicycle ergometer. Platelet aggregation, binding of von Willebrand factor (vWF) to platelets, and activation of glycoprotein (GP) IIb/IIIa and expression of P-selectin on platelets induced by shear stress were analyzed both before and immediately after exercise. Analytical results demonstrated that: (1) the levels of plasma vWF antigen and activity were enhanced after intense exercise, (2) intense exercise increased either shear- or ristocetin-induced platelet aggregation and was accompanied by an increase in vWF binding to platelets and vWF-mediated GP IIb/IIIa activation at high shear flow, and (3) shear-induced P-selectin expression in the absence or the presence of exogenous vWF was enhanced by intense exercise. Therefore, we conclude that intense exercise promotes the extent of SIPA, possibly by enhancing the ability of vWF to bind to platelets and the subsequent activation of GP IIb/IIIa complexes, as well as the expression of P-selectin in response to shear stress, which in turn may augment the risk of vascular thrombosis.
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Albert CM, Mittleman MA, Chae CU, Lee IM, Hennekens CH, Manson JE (2000) Triggering of sudden death from cardiac causes by vigorous exertion. N Engl J Med 343:1355–1361
Ault KA, Cannon CP, Mitchell J, McCahan J, Tracy RP, Novotny WF, Reimann JD, Braunwald E (1999) Platelet activation in patients after an acute coronary syndrome: results from the TIMI-12 trial. Thrombolysis in Myocardial Infarction. J Am Coll Cardiol 33:634–639
Belval T, Hellums J (1986) Analysis of shear-induced platelet aggregation with population balance mathematics. Biophys J 50:479–487
Belval T, Hellums J, Solis R (1984) The kinetics of platelet aggregation induced by fluid-shearing stress. Microvasc Res 28:279–288
Cadroy Y, Pillard F, Sakariassen KS, Thalamas C, Boneu B, Riviere D (2002) Strenuous but not moderate exercise increases the thrombotic tendency in healthy sedentary male volunteers. J Appl Physiol 93:829–833
Chow TW, Hellums JD, Moake JL, Kroll MH (1992) Shear stress-induced von Willebrand factor binding to platelet glycoprotein Ib initials calcium influx associated with aggregation. Blood 80:113–120
Dong J-F, Bernat MC, Schade A, McIntire LV, Andrews RK, Lopez JA (2001) Ristocetin-dependent, but not botrocetin-dependent, binding of von Willebrand factor to the platelet glycoprotein Ib-IX-V complex correlates with shear-dependent interactions. Blood 97:162–168
El-Sayed MS, Sale C, Jones PGW, Chester M (2000) Blood hemostasis in exercise and training. Med Sci Sports Exerc 32:918–925
Goto S, Ikeda Y, Murata M, Handa M, Takahashi E, Yoshioka A, Fujimura Y, Fukuyama M, Handa S, Ogawa S (1992) Epinephrine augments von Willebrand factor-dependent shear-induced platelet aggregation. Circulation 86:1859–1863
Goto S, Salomon DR, Ikeda Y, Ruggeri ZM (1995) Characterization of the unique mechanism mediating the shear-dependent binding of soluble von Willebrand factor to platelets. J Biol Chem 270:23352–23361
Hilberg T, Gla D, Schmidt V, Losche W, Franke G, Schneider K, Gabriel HH (2003) Short-term exercise and platelet activity, sensitivity to agonist, and platelet-leukocyte conjugate formation. Platelets 14:67–74
Holme PA, Orvim U, Hamers MJ, Solum NO, Brosstad FR, Barstad RM, Sakariassen KS (1997) Shear-induced platelet activation and platelet microparticle formation at blood flow conditions as in arteries with a severe stenosis. Arterioscler Thromb Vasc Biol 17:646–653
Ikeda Y, Handa M, Kawano K, Kamata T, Murata M, Araki Y, Anbo H, Kawai Y, Watanabe K, Itagaki I (1991) The role of von Willebrand factor and fibrinogen in platelet aggregation under varying shear stress. J Clin Invest 87:1234–1240
Kasuya N, Kishi Y, Sakita SY, Numano F, Isobe M (2002) Acute vigorous exercise primes enhanced NO release in human platelets. Atherosclerosis 161:225–232
Kestin AS, Ellis PA, Barnard MR, Errichetti A, Rosner BA, Michelson AD (1993) Effect of strenuous exercise on platelet activation state and reactivity. Circulation 88:1502–1511
Konstantopoulos K, Chow TW, Turner NA, Hellums JD, Moake JL (1997) Shear stress-induced binding of von Willebrand factor to platelet. Biorheology 34:57–71
Lee KW, Lip GY (2003) Effects of lifestyle on hemostasis, fibrinolysis, and platelet reactivity: a systematic review. Arch Intern Med 163:2368–2392
Li N, Wallen NH, Hjemdahl P (1999) Evidence for prothrombotic effects of exercise and limited protection by aspirin. Circulation 100:1374–1379
Mazzeo RS (1991) Catecholamine responses to acute and chronic exercise. Med Sci Sports Exerc 23:839–845
Merten M, Chow T, Hellums JD, Thiagarajan P (2000) A new role for P-selectin in shear-induced platelet aggregtion. Circulation 102:2045–2050
Murdock PJ, Woodhams BJ, Matthews KB, Pasi KJ, Goodall AH (1997) von Willebrand factor activity detected in a monoclonal antibody-based ELISA: an alternative to the ristocetin cofactor platelet agglutination assay for diagnostic use. Thromb Haemost 78:1272–1277
Scherer D, Kaltenbach M (1979) Frequency of lift-threatening complications associated with exercise testing. Dtsch Med Wochenschr 33:1161–1165
Siscovick DS, Weiess NS, Fletcher RH, Lasky T (1984) The incidence of primary cardiac arrest during vigorous exercise. N Engl J Med 311:874–877
Stenberg PE, McEver RP, Shuman MA, Jacques YV, Bainton DF (1985) A platelet alpha-granule membrance protein (GMP 140) is expressed to plasma membrane after activation. J Cell Biol 101:880–886
Strony J, Beaudoin A, Brands D, Adelman B (1993) Analysis of shear stress and hemodynamic factors in a model of coronary artery stenosis and thrombosis. Am J Physiol 265:H1787–H1796
Tokuue J, Hayashi J, Hata Y, Nakahara K, Ikeda Y (1996) Enhanced platelet aggregability under high shear stress after treadmill exercise in patients with effort angina. Thromb Haemost 75:833–837
Tozzi-Ciancarelli MG, Penco M, Di Massimo C (2002) Influence of acute exercise on human platelet responsiveness: possible involvement of exercise-induced oxidative stress. Eur J Appl Physiol 86:266–272
Vischer UM, Wollheim CB (1997) Epinephrine induces von Willebrand factor release from cultured endothelial cells: involvement of cyclic AMP-dependent signalling in exocytosis. Thromb Haemost 77:1182–1188
Wagner CT, Kroll MH, Chow TW, Hellums JD, Schafer AI (1996) Epinephrine and shear stress synergistically induce platelet aggregation via a mechanism that partially bypasses VWF-GP Ib interactions. Biorheology 33:209–229
Wang JS, Cheng L-J (1999) The effect of strenuous acute exercise on α2-adrenergic agonist-potentiated platelet activation. Arterioscler Thromb Vasc Biol 19:1559–1565
Wang JS, Jen CJ, Kung HC, Lin LJ, Hsiue TR, Chen HI (1994) Different effects of strenuous exercise and moderate exercise on platelet function in men. Circulation 90:2877–2885
Wang JS, Jen CJ, Chen HI (1995) Effects of exercise training and deconditioning on platelet function in men. Arterioscler Thromb Vasc Biol 15:1668–1674
Wang JS, Jen CJ, Chen HI (1997a) Effects of chronic exercise and deconditioning on platelet function in women. J Appl Physiol 83:2080–2085
Wang JS, Jen CJ, Lee H-W, Chen HI (1997b) Effects of short-term exercise on female platelet function during different phases of the menstrual cycle. Arterioscler Thromb Vasc Biol 17:1682–1686
Wang JS, Chow SE, Chen JK (2003) Strenuous, acute exercise affects reciprocal modulation of platelet and polymorphonuclear leukocyte activities under shear flow in men. J Thromb Haemost 1:2031–2037
Womack CJ, Nagelkirk PR, Coughlin AM (2003) Exercise-induced changes in coagulation and fibrinolysis in healthy populations and patients with cardiovascular disease. Sports Med 33:795–807
Acknowledgements
The study was supported by the National Science Council Grant NSC 90-2320-B-182-006. The authors would like to thank the volunteers for their enthusiastic participation in this study.
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Wang, JS. Intense exercise increases shear-induced platelet aggregation in men through enhancement of von Willbrand factor binding, glycoprotein IIb/IIIa activation, and P-selectin expression on platelets. Eur J Appl Physiol 91, 741–747 (2004). https://doi.org/10.1007/s00421-004-1050-4
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DOI: https://doi.org/10.1007/s00421-004-1050-4