Plant food delphinidin-3-glucoside significantly inhibits platelet activation and thrombosis: novel protective roles against cardiovascular diseases.
Plant food delphinidin-3-glucoside significantly inhibits platelet activation and thrombosis: novel protective roles against cardiovascular diseases.
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植物性食品 delphinidin-3-glucoside 显着抑制血小板活化和血栓形成：对心血管疾病的新保护作用。
DOI：
10.1371/journal.pone.0037323
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Ni H
中科院分区：
文献类型：
--
作者：
Yang Y;Shi Z;Reheman A;Jin JW;Li C;Wang Y;Andrews MC;Chen P;Zhu G;Ling W;Ni H
飞鸽苷-3-葡萄糖苷（Dp-3-g）是许多植物性食品中花青素的主要生物活性化合物之一。虽然一些花青素化合物已被报道对心血管疾病（cvd）有保护作用，但花青素对血小板（动脉粥样硬化血栓形成的关键角色）的直接影响尚未研究。Dp-3-g在血小板功能中的作用是完全未知的。本研究在体外和体内研究了Dp-3-g对血小板活化和几种血栓形成模型的影响。我们发现Dp-3-g在富血小板血浆和纯化血小板中显著抑制人和小鼠血小板聚集。在低剪切速率和高剪切速率下，它还能显著降低灌注室中人和小鼠血液中的血栓生长。通过活体显微镜，我们观察到Dp-3-g减少血小板沉积，使血栓不稳定，并延长血管闭塞所需的时间。Dp-3-g还能显著抑制颈动脉血栓模型中的血栓生长。为了阐明其机制，我们通过流式细胞术检测了血小板活化标志物，发现Dp-3-g显著抑制了反映血小板α-和δ-颗粒释放的p-选择素、CD63、CD40L以及细胞质蛋白分泌的表达。我们进一步证明，Dp-3-g下调血小板上活性整合素α ib β3的表达，并在激动剂治疗后减弱纤维蛋白原与血小板的结合，而不干扰纤维蛋白原与整合素α ib β3的直接相互作用。我们发现Dp-3-g降低了单磷酸腺苷活化蛋白激酶的磷酸化，这可能有助于观察到对血小板活化的抑制作用。因此，在动脉和静脉剪切应力下，Dp-3-g均能显著抑制血小板活化并减缓血栓生长，这可能有助于其对血栓形成和心血管疾病的保护作用。
Delphinidin-3-glucoside (Dp-3-g) is one of the predominant bioactive compounds of anthocyanins in many plant foods. Although several anthocyanin compounds have been reported to be protective against cardiovascular diseases (CVDs), the direct effect of anthocyanins on platelets, the key players in atherothrombosis, has not been studied. The roles of Dp-3-g in platelet function are completely unknown. The present study investigated the effects of Dp-3-g on platelet activation and several thrombosis models in vitro and in vivo. We found that Dp-3-g significantly inhibited human and murine platelet aggregation in both platelet-rich plasma and purified platelets. It also markedly reduced thrombus growth in human and murine blood in perfusion chambers at both low and high shear rates. Using intravital microscopy, we observed that Dp-3-g decreased platelet deposition, destabilized thrombi, and prolonged the time required for vessel occlusion. Dp-3-g also significantly inhibited thrombus growth in a carotid artery thrombosis model. To elucidate the mechanisms, we examined platelet activation markers via flow cytometry and found that Dp-3-g significantly inhibited the expression of P-selectin, CD63, CD40L, which reflect platelet α- and δ-granule release, and cytosol protein secretion, respectively. We further demonstrated that Dp-3-g downregulated the expression of active integrin αIIbβ3 on platelets, and attenuated fibrinogen binding to platelets following agonist treatment, without interfering with the direct interaction between fibrinogen and integrin αIIbβ3. We found that Dp-3-g reduced phosphorylation of adenosine monophosphate-activated protein kinase, which may contribute to the observed inhibitory effects on platelet activation. Thus, Dp-3-g significantly inhibits platelet activation and attenuates thrombus growth at both arterial and venous shear stresses, which likely contributes to its protective roles against thrombosis and CVDs.
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影响因子：
15.9
作者：
Hodivala-Dilke, KM;McHugh, KP;Hynes, RO
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