Blueberry Metabolites Attenuate Lipotoxicity-Induced Endothelial Dysfunction.

Blueberry Metabolites Attenuate Lipotoxicity-Induced Endothelial Dysfunction.
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DOI:
10.1002/mnfr.201700601
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发表时间:
2018-01
影响因子:
5.2
通讯作者:
Anandh Babu PV
Anandh Babu PV
中科院分区:
农林科学2区
文献类型:
--
作者:
Bharat D;Cavalcanti RRM;Petersen C;Begaye N;Cutler BR;Costa MMA;Ramos RKLG;Ferreira MR;Li Y;Bharath LP;Toolson E;Sebahar P;Looper RE;Jalili T;Rajasekaran NS;Jia Z;Symons JD;Anandh Babu PV

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脂毒性诱导的内皮功能障碍是与糖尿病相关的重要血管并发症。临床研究支持蓝莓花青素对血管的益处,但其潜在机制尚不清楚。测试了蓝莓花青素代谢物减轻脂毒性诱导的内皮功能障碍的假设。人主动脉内皮细胞 (HAEC) 用以下任一物质处理 6 小时: (i) 母体花青素(锦葵素-3-葡萄糖苷和花青素-3-葡萄糖苷); (ii) 蓝莓代谢物(羟基马尿酸、马尿酸、4-硫酸苯甲酸、3-硫酸异香草酸和 4-硫酸香草酸),其浓度已知在食用蓝莓后在人体中循环。最后 5 小时用棕榈酸酯或媒介物处理 HAEC。用棕榈酸酯处理的 HAEC 表现出活性氧生成增加,NOX4、趋化因子、粘附分子和 IκBα 的 mRNA 表达增加,单核细胞结合增强,并抑制一氧化氮产生。值得注意的是,在用蓝莓代谢物处理的 HAEC 中,棕榈酸酯的破坏作用得到了改善,但亲本花青素却没有得到改善。此外,我们的观察提供了这些结果的重要翻译相关性,即在与蓝莓代谢物同时孵育的动脉段中,棕榈酸诱导的内皮功能障碍减轻。研究结果表明,蓝莓花青素对血管的益处是由其代谢物介导的。蓝莓可能会补充现有疗法以减少血管并发症。
Lipotoxicity-induced endothelial dysfunction is an important vascular complication associated with diabetes. Clinical studies support the vascular benefits of blueberry anthocyanins, but the underlying mechanism is unclear. The hypothesis that metabolites of blueberry anthocyanins attenuate lipotoxicity-induced endothelial dysfunction was tested. Human aortic endothelial cells (HAECs) were treated for 6 h with either: (i) the parent anthocyanins (malvidin-3-glucoside and cyanidin-3-glucoside); or (ii) the blueberry metabolites (hydroxyhippuric acid, hippuric acid, benzoic acid-4-sulfate, isovanillic acid-3-sulfate, and vanillic acid-4-sulfate), at concentrations known to circulate in humans following blueberry consumption. For the last 5 h HAECs were treated with palmitate or vehicle. HAECs treated with palmitate displayed elevated reactive oxygen species generation, increased mRNA expression of NOX4, chemokines, adhesion molecules, and IκBα, exaggerated monocyte binding, and suppressed nitric oxide production. Of note, the damaging effects of palmitate were ameliorated in HAECs treated with blueberry metabolites but not parent anthocyanins. Further, important translational relevance of these results was provided by our observation that palmitate-induced endothelial dysfunction was lessened in arterial segments that incubated concurrently with blueberry metabolites. The presented findings indicate that the vascular benefits of blueberry anthocyanins are mediated by their metabolites. Blueberries might complement existing therapies to lessen vascular complications.
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