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.


METHODS
We measured aggregation, changes in cytosolic Ca(2+) 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 Ca(2+) 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.
de Lange
Dylan W
DW
Thrombosis and Haemostasis Laboratory, Department of Clinical Chemistry and Haematology, University Medical Center-Utrecht, Utrecht, The Netherlands. D.W.deLange@umcutrecht.nl
Verhoef
Sandra
S
Gorter
Gertie
G
Kraaijenhagen
Rob J
RJ
van de Wiel
Albert
A
Akkerman
Jan-Willem N
JW
D000244:Adenosine Diphosphate / Q000494:pharmacology; D001711:Biotransformation / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D003600:Cytosol / Q000378:metabolism; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology*; D005602:France / Q000453:epidemiology; D005638:Fruit / Q000737:chemistry; D006801:Humans; D007202:Indicators and Reagents; D010636:Phenols / Q000302:isolation & purification / Q000494:pharmacology*; D010766:Phosphorylation; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism / Q000502:physiology*; D059808:Polyphenols; D018179:Receptors, Thrombin / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D027843:Vitis / Q000737:chemistry*; D014920:Wine
D005419:Flavonoids; D007202:Indicators and Reagents; D010636:Phenols; D010936:Plant Extracts; D010975:Platelet Aggregation Inhibitors; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D059808:Polyphenols; D018179:Receptors, Thrombin; D014443:Tyrosine; D000244:Adenosine Diphosphate; D002118:Calcium