Objective-Alternating shear stress, which resembles the flow condition in stenotic arteries, induces platelet aggregation.This study investigated how exercise training and deconditioning influence alternating shear-induced platelet aggregation (ASIPA) and clarify the mechanisms underlying ASIPA. Methods and Results-Thirty healthy male sedentary subjects were randomly divided into control and trained groups. The trained men were trained on a bicycle ergometer at Ϸ60% of maximal oxygen consumption for 30 minutes per day, 5 days per week for 8 weeks, and then were deconditioned for 8 weeks. The experimental results indicate the following:(1) short-term strenuous exercise increases the extent of ASIPA and is accompanied by increased the von Willebrand factor (vWF) binding and P-selectin expression on platelets in both the control and trained groups, whereas the enhancement of platelet function decreases after exercise training in trained subjects; (2) at rest and immediately after exercise, ASIPA and the vWF binding and P-selectin expression on platelets are reduced by training, but remain unchanged in the control group; and (3) Key Words: training Ⅲ detraining Ⅲ shear stress Ⅲ platelets Ⅲ adhesion molecules L ifestyle habits such as exercise may have significant influence on the risk of major vascular thrombotic events. 1,2 Previous studies have suggested that the risk of primary cardiac arrest transiently increases during vigorous exercise, 3,4 whereas regular exercise is associated with an overall decreased risk of cardiovascular diseases. 5,6 Shear-induced platelet aggregation (SIPA) is important in arterial thrombosis, which is a major contributing factor for atherothrombotic occlusion of blood vessels. 7 Therefore, it is important to distinguish the shearmediated thrombotic events that occur between short-term bouts of exercise and physical conditioning. According to our earlier study of male patients with stable angina, strenuous acute exercise can increase the capacity of adhered platelets to withstand physiological flow shear stress. 8 A previous investigation also demonstrated that SIPA increased after strenuous treadmill exercise in patients with effort angina. 9 However, the effects of exercise training and detraining on shearmediated platelet activation and its underlying mechanisms have not yet been studied. See page 265Pathological, high shear stress induces binding of von Willebrand factor (vWF) to the platelet glycoprotein (GP) Ib complex on platelets. This interaction transduces signals in platelets, subsequently activating GP IIb/IIIa complex. The activated GP IIb/IIIa complex then binds to fibrinogen, stabilizing the aggregated platelets. 10,11 Our recent investigation showed that short-term intense exercise promoted SIPA, possibly by improving the ability of vWF to bind to platelets and the subsequent activation of GPIIb/IIIa complexes to sustained high shear stress. 12 In fact, blood flow in stenotic vessel follows a complex pattern of hydrodynamics in that flow rate first increases dramatical...