Schizandrin B attenuates angiotensin II induced endothelial to mesenchymal transition in vascular endothelium by suppressing NF-κB activation
Schizandrin B attenuates angiotensin II induced endothelial to mesenchymal transition in vascular endothelium by suppressing NF-κB activation
复制标题
五味子素 B 通过抑制 NF-κ B 激活来减弱血管紧张素 II 诱导的血管内皮细胞向间质转化
DOI：
10.1016/j.phymed.2019.152955
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发表时间：
2019-09-01
期刊：
影响因子：
7.9
通讯作者：
Liang Guang
中科院分区：
文献类型：
--
作者：
You Shengban;Qian Jianchang;Liang Guang
背景资料：血管紧张素II（AngII）诱导的慢性炎症和氧化应激常常导致不可逆的血管损伤，其中涉及内皮层中的内皮向间质转化（EndMT）。五味子醇甲B（Sch B）是从传统五味子中提取的天然产物，具有血管保护作用，但其作用机制尚不清楚，本研究旨在探讨Sch B对血管紧张素II（Ang II）诱导的血管损伤的保护作用及其机制。在体外，Ang II诱导的HUVECs的损伤，以研究其潜在的机制。结果：预先给予Sch B可有效地减轻Ang II处理动物的血管EndMT表型和纤维化，同时降低炎性细胞因子和ROS。来自HUVECs的体外数据表明，Sch B直接靶向NF-κ B活化以抑制Ang II诱导的EndMT和血管损伤。在Ang II存在下，EndMT的活化受NF-κ B调节，NF-κ B是炎症和氧化应激中的常见参与者。结论：Ang Ⅱ诱导的小鼠血管内皮细胞损伤与EndMT有关，而Sch B通过抑制NF-κ B的活化可以抑制炎症/ROS介导的EndMT。这些结果也意味着NF-κ B B可能是通过EndMT机制减轻炎症和氧化应激诱导的血管重塑的有希望的靶点。
Background: Angiotensin II (Ang II)-induced chronic inflammation and oxidative stress often leads to irreversible vascular injury, in which the endothelial to mesenchymal transition (EndMT) in the endothelial layers are involved. Schisandrin B (Sch B), a natural product isolated from traditional Schisandra chinensis, has been reported to exert vascular protective properties with unclear mechanism.Hypothesis/purpose: This study investigated the protective effects and mechanism of Sch B against Ang II-induced vascular injury.Methods: C57BL/6 mice were subcutaneous injected of Ang II for 4 weeks to induce irreversible vascular injury. In vitro, Ang II-induced HUVECs injury was used to study the underlying mechanism. The markers of EndMT, inflammation and oxidative stress were studied both in vitro and in vivo.Results: Pre-administration of Sch B effectively attenuated phenotypes of vascular EndMT and fibrosis in Ang II-treated animals, accompanied with decreased inflammatory cytokine and ROS. The in vitro data from HUVECs suggest that Sch B directly targets NF-kappa B activation to suppress Ang II-induced EndMT and vascular injury. The activation of EndMT in the presence of Ang II is regulated by the NF-kappa B, a common player in inflammation and oxidative stress. Ang II-induced inflammation and oxidative stress also contributed to vascular EndMT development and Sch B inhibited inflammation/ROS-mediated EndMT by suppressing NF-kappa B.Conclusion: EndMT contributes to vascular injury in Ang II-treated mice, and it can be prevented via suppressing NF-kappa B activation by Sch B treatment. These results also imply that NF-kappa B might be a promising target to attenuate vascular remodeling induced by inflammation and oxidative stress through an EndMT mechanism.