Polyphenolic grape extract inhibits platelet activation through PECAM-1: An explanation for the French paradox

Background: Moderate and prolonged consumption of red wine is associated with decreased cardiovascular morbidity and mortality. Inhibition of platelet functions by ingredients in red wine is thought to be one of the causes. However, the molecular mechanism of this inhibition has remained unexplained. Materials and Methods: We measured aggregation, changes in cytosolic Ca2+ and tyrosine phosphorylation of the inhibitory receptor platelet endothelial cell adhesion molecule-1 (PECAM-1) in platelets stimulated with thrombin receptor (PAR-1) activating peptide (TRAP) and ADP and investigated the effects of alcohol-free polyphenolic grape extract (PGE), alcohol, and the polyphenols catechin, epi-catechin, resveratrol, trans-resveratrol, and gallic acid. Results: Polyphenolic grape extract induced dose-dependent inhibition of TRAP-induced and ADP-induced platelet aggregation and Ca2+ mobilization. Inhibition was accompanied by activation of PECAM-1. Apart from a slight inhibition by catechin, ethanol or other individual polyphenols failed to inhibit aggregation or activate PECAM-1. Conclusions: Red wine inhibits platelet functions through its PGE content, which stimulates the inhibitory receptor PECAM-1, thereby attenuating platelet activation.