Resveratrol decreases early signaling events in washed platelets but has little effect on platelet aggregation in whole blood

Resveratrol, a polyphenolic compound found in red wines, is believed to be a contributor in decreasing the incidence of coronary heart disease. Althou gh its primary target is unknown, it blocks aggregation of washed platelets by an ill-defined mechanism. We show that resveratrol, at 10-50 mu M, bloc ked aggregation induced by collagen (5 mu g/ml), thrombin (0.2 units/ml), a nd ADP (10 mu M). This affect was not overcome by adding exogenous human fi brinogen to the assay, suggesting that an early (wave I) signaling step in the alpha(IIB)beta(3) activation cascade was impaired. To explore this poss ibility we examined the effect of resveratrol on activation of MAP kinases. In the platelet, MAP kinases become activated as a consequence of agonist binding and not of aggregation, which itself induces signaling events. In f act, we find that collagen-induced activation of MAP kinases is superinduce d in the presence of RGDS, an aggregation-blocking peptide. Resveratrol, at concentrations of 10 mu M and greater, inhibited MAP kinase activation ind uced by collagen (in the absence and presence of RGDS peptide), thrombin, a nd ADP. These data indicate that resveratrol blocks receptor-mediated signa ling events in washed platelets. In comparison, resveratrol has poor antipl atelet activity in whole blood. Under these conditions aggregation was not affected by 50-100 mu M resveratrol. Concentrations of 200 mu M resveratrol were needed to cause a 30-60% decrease in platelet aggregation in whole bl ood. Together these studies suggest that resveratrol is a potent inhibitor of platelet signaling responses, but its antiplatelet activity is weakened or masked in circulation. Thus, although resveratrol may function as a prot ective agent of coronary heart disease, its affects are not solely attribut ed to its effects on platelets in circulation, (C) 2000 Academic Press.