Liver X Receptor Agonist Alleviated High Glucose-Induced Endothelial Progenitor Cell Dysfunction via Inhibition of Reactive Oxygen Species and Activation of AMP-Activated Protein Kinase
Liver X Receptor Agonist Alleviated High Glucose-Induced Endothelial Progenitor Cell Dysfunction via Inhibition of Reactive Oxygen Species and Activation of AMP-Activated Protein Kinase
复制标题
肝脏 X 受体激动剂通过抑制活性氧和激活 AMP 激活蛋白激酶来减轻高葡萄糖诱导的内皮祖细胞功能障碍
DOI：
10.1111/j.1549-8719.2012.00186.x
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发表时间：
2012-08-01
期刊：
影响因子：
2.4
通讯作者：
Zhu, Yi
中科院分区：
文献类型：
--
作者：
Li, Xiaoxia;Song, Yimeng;Zhu, Yi
请引用本文为：李X，宋Y，韩Y，王D，朱Y。肝X受体激动剂通过抑制活性氧和激活AMP活化蛋白激酶减轻高糖诱导的内皮祖细胞功能障碍。微循环与19：547553，2012相似。摘要目的：肝X受体（LXRs）是胆固醇稳态的关键调节因子。合成的LXR激动剂具有抗动脉粥样硬化和抗炎作用。然而，LXR激动剂对内皮祖细胞（EPC）功能的影响在很大程度上是未知的。在这里，我们探讨了LXR激动剂TO901317（TO）对EPC生物学的影响及其机制。方法：内皮祖细胞在甘露醇或30 mM葡萄糖（高糖）中培养24小时。对于TO处理，细胞用TO（10 μ m）预处理12小时，然后加入甘露醇或高浓度葡萄糖再处理24小时。分析EPCs功能、活性氧（ROS）释放和腺苷一磷酸活化蛋白激酶（AMPK）磷酸化。结果：TO可恢复高糖损伤的EPCs粘附和迁移能力。高糖损害EPC介导的血管生成，和TO逆转的损害。TO还能减轻高糖诱导的ROS释放。Western blot分析显示，高糖下调AMPK和内皮型一氧化氮合酶的磷酸化，这可以逆转与TO治疗。此外，化合物C抑制AMPK活化可取消TO对EPCs的保护作用。结论：TO通过抑制ROS释放和激活AMPK对高糖环境下EPCs具有保护作用。
Please cite this paper as: Li X, Song Y, Han Y, Wang D, Zhu Y. Liver X receptor agonist alleviated high glucose-induced endothelial progenitor cell dysfunction via inhibition of reactive oxygen species and activation of AMP-activated protein kinase. Microcirculation similar to 19: 547553, 2012. Abstract Objective: Liver X receptors (LXRs) are key regulators of cholesterol homeostasis. Synthetic LXR agonists are anti-atherogenic and anti-inflammatory. However, the effect of LXR agonists on endothelial progenitor cell (EPC) function is largely unknown. Here, we explored the effect of the LXR agonist TO901317 (TO) on EPC biology and the underlying mechanisms. Methods: Endothelial progenitor cells were cultured in mannitol or 30 mm glucose (high glucose) for 24 hours. For TO treatments, cells were pretreated with TO (10 mu m) for 12 hours, then mannitol or high glucose was added for an additional 24 hours. EPCs function, reactive oxygen species (ROS) release, and phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) were analyzed. Results: TO could restore the high glucose-impaired adhesion and migration capacity of EPCs. High glucose impaired EPC-mediated angiogenesis, and TO reversed the impairment. TO also alleviated ROS release induced by high glucose. Western blot analysis revealed that high glucose downregulated the phosphorylation of AMPK and endothelial nitric oxide synthase, which could be reversed with TO treatment. Furthermore, inhibiting AMPK activation by compound C could abolish the protective effects of TO on EPCs. Conclusions: TO had a protective effect on EPCs under high glucose by inhibiting ROS release and activating AMPK.