1Department of Clinical and Laboratory Medicine, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
Clin Appl Thromb Hemost. 2014 Apr;20(3):278-84. doi: 10.1177/1076029613481103. Epub 2013 Mar 10.
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.
血小板在各种血栓性疾病中发挥着重要作用，包括心肌梗死。由于红酒的消费与因缺血性心脏病导致的死亡呈负相关，因此葡萄成分对血小板功能的影响已被广泛研究。葡萄种子提取物（GSE）据报道可抑制血小板聚集；然而，其潜在机制尚未阐明。我们发现 GSE 可抑制胶原和凝血酶受体激动肽诱导的血小板聚集，并增加酪氨酸磷酸化的基础水平，这在存在蛋白酪氨酸磷酸酶（PTP）抑制剂的情况下也观察到。体外磷酸酶测定表明，GSE 剂量依赖性地抑制 PTP-1B 和含 SH2 结构域的磷酸酶-1 的活性，而后者可正向调节血小板聚集。我们提出，GSE 通过抑制酪氨酸磷酸酶活性来抑制血小板聚集。此外，我们表明 GSE 摄入可抑制小鼠的血小板聚集而不增加尾部出血，这表明 GSE 补充可能有益于预防血栓性疾病。
