Background: Many natural compounds, including polyphenols, isolated from different plants are characterized by anti-inflammatory and antithrombotic properties and they are often used to reduce the risk of cardiovascular disease. Resveratrol is a natural polyphenol that exhibits many therapeutic effects including inhibition of platelet activation; however the molecular mechanism of its action on platelets is not fully defined.

Aims: Because cyclic nucleotides (cAMP, cGMP) and corresponding protein kinases (PKA, PKG) are the main intracellular platelet inhibitory mechanisms, we tested whether platelet inhibition by resveratrol is mediated by activation of these pathways, or by other mechanisms.  

Methods: Platelets were activated by thrombin and collagen-related peptide (CRP). Flow cytometry was used to assess platelet activation (Fibrinogen-Alexa-647), platelet viability (Calcein-AM), and reactive oxygen species (ROS) formation (DCF-DA). Activity of kinases involved in platelet stimulatory pathways PKB ERK1,2 were analyzed by Western blotting. Caspase3 activation was used as a marker of apoptosis. Phosphorylation of the Vasodilator-stimulated protein (VASP) was used as a marker of these kinases activation.

Results: Resveratrol showed a dose-dependent inhibition of washed platelets activation induced by thrombin or CRP followed by diminished phosphorylation of PKB and Erk. Resveratrol, even at high concertation (100 µM) did not induce VASP phosphorylation, indicating that its inhibitory effect is not mediated by PKA/PKG activation. Platelet inhibition also could be connected with initiation of apoptosis, or reduction of platelet viability. Therefore, we tested whether resveratrol activates caspase-dependent apoptosis or induces platelet death. Resveratrol in all tested concentrations (1 -100 µM) had no effect on caspase3 activation and platelet viability. ROS are involved in platelet activatory pathways and CRP and thrombin strongly initiated ROS production in platelets. Resveratrol concentration-dependently inhibited ROS formation induced by CRP and thrombin.

Conclusions: All our data indicated that inhibitory effects of resveratrol in platelet activation are mainly mediated by the prevention of ROS formation.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/resveratrol-prevents-platelet-activation-by-inhibition-of-ros-formation/