Xyloketal B attenuates atherosclerotic plaque formation and endothelial dysfunction in apolipoprotein e deficient mice.
Xyloketal B attenuates atherosclerotic plaque formation and endothelial dysfunction in apolipoprotein e deficient mice.
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Xyloketal B 减轻载脂蛋白 E 缺陷小鼠的动脉粥样硬化斑块形成和内皮功能障碍
DOI：
10.3390/md13042306
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发表时间：
2015-04-14
期刊：
影响因子：
5.4
通讯作者：
Wang GL
中科院分区：
文献类型：
--
作者：
Zhao LY;Li J;Yuan F;Li M;Zhang Q;Huang YY;Pang JY;Zhang B;Sun FY;Sun HS;Li Q;Cao L;Xie Y;Lin YC;Liu J;Tan HM;Wang GL
我们前期的研究表明，具有独特化学结构的新型海洋化合物木缩酮B具有较强的抗氧化作用，在体外培养的不同类型细胞和体内模型生物中均能保护内皮细胞免受损伤。氧化内皮功能障碍和一氧化氮（NO）生物利用度降低是动脉粥样硬化病变发展的关键。因此，我们研究了木缩酮B是否对高脂饮食喂养的载脂蛋白E缺陷（apoE−/−）小鼠的动脉粥样硬化斑块面积有影响，并研究了潜在的机制。我们在目前的研究中发现，给予木糖缩酮B可剂量依赖性地减少高脂饮食apoE−/−小鼠主动脉窦和整个主动脉的动脉粥样硬化斑块面积。此外，木糖缩酮B显著降低血管氧化应激水平，改善动脉粥样硬化小鼠受损的内皮完整性和NO依赖性主动脉血管舒张。此外，木缩酮B显着改变内皮型一氧化氮合酶（eNOS）和Akt的磷酸化水平，而不改变总eNOS和Akt在培养的人脐静脉内皮细胞（HUVECs）的表达。在这里，它增加了Ser-1177正调节位点的eNOS磷酸化，同时抑制Thr-495负调节位点的磷酸化。总之，这些发现表明，木糖缩酮B在体内具有显著的抗动脉粥样硬化作用，这部分是由于其抗氧化特征和/或改善内皮功能。
Our previous studies demonstrated that xyloketal B, a novel marine compound with a unique chemical structure, has strong antioxidant actions and can protect against endothelial injury in different cell types cultured in vitro and model organisms in vivo. The oxidative endothelial dysfunction and decrease in nitric oxide (NO) bioavailability are critical for the development of atherosclerotic lesion. We thus examined whether xyloketal B had an influence on the atherosclerotic plaque area in apolipoprotein E-deficient (apoE−/−) mice fed a high-fat diet and investigated the underlying mechanisms. We found in our present study that the administration of xyloketal B dose-dependently decreased the atherosclerotic plaque area both in the aortic sinus and throughout the aorta in apoE−/− mice fed a high-fat diet. In addition, xyloketal B markedly reduced the levels of vascular oxidative stress, as well as improving the impaired endothelium integrity and NO-dependent aortic vasorelaxation in atherosclerotic mice. Moreover, xyloketal B significantly changed the phosphorylation levels of endothelial nitric oxide synthase (eNOS) and Akt without altering the expression of total eNOS and Akt in cultured human umbilical vein endothelial cells (HUVECs). Here, it increased eNOS phosphorylation at the positive regulatory site of Ser-1177, while inhibiting phosphorylation at the negative regulatory site of Thr-495. Taken together, these findings indicate that xyloketal B has dramatic anti-atherosclerotic effects in vivo, which is partly due to its antioxidant features and/or improvement of endothelial function.
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影响因子：
2.9
作者：
Lu, Xi-lin;Yao, Xiao-li;Zeng, Jinsheng
通讯作者：
Zeng, Jinsheng
影响因子：
64.8
作者：
Dimmeler, S;Fleming, I;Zeiher, AM
通讯作者：
Zeiher, AM
影响因子：
8.3
作者：
Domagala, Teresa B.;Szeffler, Agata;Kalinowski, Leszek
通讯作者：
Kalinowski, Leszek
影响因子：
6.9
作者：
Dake, Brian L.;Oltman, Christine L.
通讯作者：
Oltman, Christine L.
影响因子：
2.8
作者：
Leone, Aurelio;Balbarini, Alberto
通讯作者：
Balbarini, Alberto