Reducing state attenuates ectodomain shedding of GPVI while restoring adhesion capacities of stored platelets: evidence addressing the controversy around the effects of redox condition on thrombosis.

摘要: Thrombosis involves different stages including platelet adhesion to the site of injury, aggregatory events governed by integrin activation, pro-inflammatory responses recruiting leukocytes and finally, pro-coagulant activity which results in fibrin generation clot formation. As important signaling agents, reactive oxygen species (ROS) reduce thrombus volume growth, however given such a multistage mechanism, it is not well-elucidated how ROS inhibition modulates thrombosis. PRP-platelet concentrates (PCs) were either treated with ROS-reducing agents (1 mM NAC or 30 μM NOX inhibitor, VAS2870) kept untreated during storage. Shedding expression receptors presence inhibitors, agonists CCCP (as controls) analyzed flow cytometery western blot respectively. Besides above parameters, collagen stored platelets was examined inhibitors using fluorescence-microscopy. Highest levels shedding achieved ionophore while induces much more GPVI than that GPIbα. reduced from day 3 storage enhanced their expressions. only did capacity but also (in NAC) spreading 5 days-stored PCs. While reducing state significantly inhibits aggregation our indicated as first stage thrombosis, resistance inhibitory effects. These findings highlight fact integrin-dependent activation vulnerable GPVI-dependent adhesion. Presumably, activating signals preserves adhesiveness due lessening shedding.