title: Grape seed extracts inhibit platelet aggregation by inhibiting protein tyrosine phosphatase.
abstract: Platelets play an important role in various thrombotic diseases, including myocardial infarction. Because red wine consumption is inversely associated with death due to ischemic heart diseases, the effects of grape components on platelet function have been extensively investigated. Grape seed extracts (GSEs) reportedly inhibit platelet aggregation; however, the underlying mechanism has not been elucidated. We discovered that GSEs inhibit platelet aggregation induced by collagen and thrombin-receptor agonist peptide and increase basal levels of tyrosine phosphorylation, which was also observed in the presence of a protein tyrosine phosphatase (PTP) inhibitor. An in vitro phosphatase assay indicated that GSE dose dependently inhibited PTP-1B and Src homology 2 domain-containing phosphatase-1 activity, which positively regulates platelet aggregation. We propose that GSEs inhibit platelet aggregation by inhibiting tyrosine phosphatase activity. Moreover, we showed that GSE ingestion inhibited platelet aggregation in mice without enhancing tail bleeding, implying that GSE supplementation might be beneficial to prevention of thrombotic diseases.
authors.affiliation: 1Department of Clinical and Laboratory Medicine, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
authors.forename: Joseph Wuxun
authors.initials: JW
authors.lastname: Jin
authors.forename: Osamu
authors.initials: O
authors.lastname: Inoue
authors.forename: Katsue
authors.initials: K
authors.lastname: Suzuki-Inoue
authors.forename: Go
authors.initials: G
authors.lastname: Nishikawa
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kawakami
authors.forename: Masashi
authors.initials: M
authors.lastname: Hisamoto
authors.forename: Tohru
authors.initials: T
authors.lastname: Okuda
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ozaki
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D056604:Grape Seed Extract / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects*; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D056604:Grape Seed Extract; D017027:Protein Tyrosine Phosphatases
keywords: collagen; grape seed extracts; platelets; polyphenols; protein tyrosine phosphatase; protein tyrosine phosphorylation