Cocoa and wine polyphenols modulate platelet activation and function.
There is speculation that dietary polyphenols can provide cardioprotective effects due to direct antioxidant or antithrombotic mechanisms. We report in vitro and postingestion ex vivo effects of cocoa procyanidins, a procyanidin-rich cocoa beverage and dealcoholized red wine (DRW) on human platelet activation. In a series of in vitro studies, cocoa procyanidin trimers, pentamers or DRW (3 and 10 micromol/L) were incubated with citrated peripheral whole blood in the presence and absence of platelet agonists. Platelet activation was detected using fluorescent-labeled monoclonal antibodies recognizing the fibrinogen binding conformation of GPIIb-IIIa (referred to herein as PAC-1 binding) and the activation-dependent platelet epitope CD62P (P-selectin). The percentage of CD42a-positive platelets coexpressing PAC-1 binding and/or CD62P was determined by multiparameter flow cytometry. Procyanidin trimers, pentamers and DRW added to whole blood in vitro increased PAC-1 binding and P-selectin expression. In contrast, procyanidin trimers, pentamers and DRW inhibited the platelet activation in response to epinephrine. The effects on platelet activation of cocoa beverage and DRW consumption were also studied in healthy subjects. Citrated blood was obtained before and 2 and 6 h after the ingestion of a cocoa beverage, a caffeine-containing beverage, DRW or water. Platelet activation was measured by flow cytometry. The consumption of DRW did not affect the expression of activation-dependent platelet antigens, either unstimulated or after ex vivo activation with epinephrine. However, the consumption of DRW increased PAC-1 binding in response to 100 micromol/L ADP ex vivo. Cocoa consumption reduced platelet response to agonists ex vivo. The ingestion of water had no effect on platelet activation, whereas a caffeine-containing beverage augmented the response of platelets to epinephrine. In summary, select cocoa procyanidins and DRW added to whole blood in vitro increased expression of platelet activation markers in unstimulated platelets but suppressed the platelet activation response to epinephrine. In contrast, cocoa consumption suppressed unstimulated and stimulated platelet activation in whole blood. This suppressive effect observed on platelet reactivity may explain in part the reported cardioprotective effects of dietary polyphenols.
Department of Nutrition, University of California, Davis, Davis, CA 95616, USA.
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Rein
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Paglieroni
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Pearson
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Wun
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Schmitz
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Gosselin
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Keen
D000328:Adult; D000704:Analysis of Variance; D002099:Cacao / Q000502:physiology*; D002110:Caffeine / Q000008:administration & dosage / Q000494:pharmacology*; D016022:Case-Control Studies; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D054641:Dual Specificity Phosphatase 2; D005260:Female; D005419:Flavonoids; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D015539:Platelet Activation / Q000187:drug effects*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D011108:Polymers / Q000494:pharmacology*; D059808:Polyphenols; D054648:Protein Phosphatase 2; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D014920:Wine
D000697:Central Nervous System Stimulants; D005419:Flavonoids; D019007:P-Selectin; D010636:Phenols; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011108:Polymers; D059808:Polyphenols; D002110:Caffeine; D054648:Protein Phosphatase 2; C517032:DUSP2 protein, human; D054641:Dual Specificity Phosphatase 2; D017027:Protein Tyrosine Phosphatases