The inhibitory action of quercetin on GPVI-mediated platelet signaling and activation
Abstract number: P0220
Hubbard G., Stevens J. M., Sage T., Jordan P. A., Lovegrove J. L., Gibbins J. M.
University of Reading, UK
The regulation of platelet function by pharmacological agents that modulate platelet signaling has proven a successful approach to the prevention of thrombosis. A variety of molecules present in the diet have been shown to inhibit platelet activation. The compound quercetin is a dietary antioxidant with a polyphenolic structure that is present in many foods, such as onion, apples, wine and tea, and an increased intake of quercetin has been correlated with a decrease in the risk of cardiovascular disease. Quercetin has been reported to exhibit a wide range of biological and pharmacological effects in animals and man that include the inhibition of various enzymes and enzyme systems, as well as the inhibition of platelet aggregation. In this report, we investigate the molecular mechanisms through which quercetin inhibits collagen-stimulated platelet aggregation. Quercetin inhibits collagen-stimulated platelet aggregation, intracellular mobilization of calcium and whole cell protein tyrosine phosphorylation, in a concentration-dependant manner. Quercetin was also found to inhibit various events in signaling generated by the collagen receptor glycoprotein VI (GPVI). This includes collagen-stimulated tyrosine phosphorylation of the Fc receptor gamma-chain, Syk, LAT and Phospholipase C gamma2. Inhibition of phosphorylation of the Fc receptor gamma-chain suggests that quercetin inhibits early signaling events following stimulation of platelets with collagen. The activity of the kinases that phosphorylate the Fc receptor gamma-chain, Fyn and Lyn, as well as the tyrosine kinase Syk and phosphoinositide 3-kinase were also inhibited by quercetin in a concentration-dependant manner, both in whole cells and in isolation. The present results provide a molecular basis for the inhibition by quercetin of collagen-stimulated platelet activation, through inhibition of multiple components of the GPVI signaling pathway, and may begin to explain the proposed health benefits of high-quercetin intake.
To cite this abstract use the following format:
Journal of Thrombosis and Haemostasis 2003; 1 Supplement 1 July: abstract number
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