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

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.

Changes in Endothelial Markers during a Summer Ultra-Endurance Road Cycling Event in the Heat

“…It has been suggested that age is associated with greater concentrations of p-selectin immediately following prolonged endurance exercise events [13]. The 28% increase in p-selectin concentrations from PRE to IP observed in the present study supports previous findings of exercise-induced activation of the endothelium [13,27], and adds to these findings by demonstrating that this activation is also present after prolonged cycling in the heat. However, unlike Parker et al [13], we found no relationship between changes in p-selectin and changes in age of the riders in our study.…”

“…One of these parameters is p-selectin, which is primarily located in endothelium cells and storage granules in platelets and translocated to the cell surface upon activation of the endothelium [24]. The concentrations of p-selectin is increased in individuals with various immunological, inflammatory, and cardiovascular disease ( [25,26] and increases after high intensity exercise [13,27]. It has been suggested that age is associated with greater concentrations of p-selectin immediately following prolonged endurance exercise events [13].…”

Exercise prescription and thrombogenesis

“…A number of thrombotic modifications have been reported in acute exercise, exercise training, and physical deconditioning/inactivity. Based on research to date, this study attempted to summarize the effects of acute exercise on platelets, coagulation and fibrinolysis as follows: light, acute exercise (i.e., £ 49%VO 2max , £ 59%HR max , £ 11 on the RPE scale, £ 4 MTEs) does not sufficiently [18,[20][21][22]29]. e > 83% VO 2max [61].…”

“…Shear stress levels in stenotic arteries reach from 60 to 3300 dynes/cm 2 [28]. By simulating flow conditions in stenotic arteries using a rotational viscometer, measurement results from previous studies by the authors demonstrated that strenuous exercise (80% VO 2max for 40 min) enhanced platelet aggregation under high shear stress (100 dyne/cm 2 ), possibly by improving the ability of von Willbrand factor (vWF) binding to platelets and, subsequently, activating glycoprotein IIb/IIIa (GPIIb/IIIa) and P-selectin expression on platelets [29]. Furthermore, a clinical investigation also displayed that shearinduced platelet aggregation in patients with effort angina enhanced after strenuous treadmill exercise [30].…”

“…An early study indicated that strenuous exercise improved performance of platelet a 2 -adrenergic receptors by increasing endogenous release of epinephrine, thereby promoting activation of fibrinogen receptors (as GP IIb/IIIa complex) and fibrinogen binding to platelet fibrinogen receptors [20]. Additionally, strenuous exercise also enhanced a 2 -adrenergic receptor-mediated platelet [Ca 2+ ] i elevation, suggesting that exocytosis of a-granules and subsequent translocation of P-selectin in platelet may be increased by strenuous exercise [20,29]. Therefore, the endogenous release of epinephrine and activation of platelet a 2 -adrenergic receptor induced by strenuous exercise can be partially explained by enhanced shearinduced platelet aggregation via the vWF-GPIb interaction, GPIIb/IIIa activation, and P-selectin expression during strenuous exercise.…”