Activation of Nrf2 Attenuates Pulmonary Vascular Remodeling via Inhibiting Endothelial-to-Mesenchymal Transition: an Insight from a Plant Polyphenol.
Activation of Nrf2 Attenuates Pulmonary Vascular Remodeling via Inhibiting Endothelial-to-Mesenchymal Transition: an Insight from a Plant Polyphenol.
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Nrf2 的激活通过抑制内皮向间质转化来减弱肺血管重塑：来自植物多酚的见解
DOI：
10.7150/ijbs.20316
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发表时间：
2017
影响因子：
9.2
通讯作者：
Du G
中科院分区：
文献类型：
--
作者：
Chen Y;Yuan T;Zhang H;Yan Y;Wang D;Fang L;Lu Y;Du G
内皮-间质转化（EndMT）参与肺血管重构。其部分归因于内皮细胞中的氧化和炎症应激。本研究通过一系列的实验来阐明丹参素酸A（salvioleticacid A，SAA）在人肺动脉内皮细胞EndMT过程中的作用，以及在体对野百合碱（monocrotaline，MCT）诱导的EndMT血管重构的治疗作用。用TGFβ1诱导人肺动脉内皮细胞（HPAECs）产生EndMT。SAA可显着减弱EndMT，同时抑制细胞迁移和活性氧簇（ROS）的形成。SAA能改善MCT诱导的肺动脉高压（PAH）模型的血管功能，降低TGFβ1水平，抑制炎症反应。从机制上讲，SAA刺激Nrf 2易位和随后的血红素加氧酶-1（HO-1）上调。SAA对EndMT的作用可被HO-1抑制剂ZnPP阻断。总之，本研究表明氧化应激对EndMT的有害影响。多酚类抗氧化剂治疗可能通过抑制EndMT而减轻肺血管重构。
The endothelial-to-mesenchymal transition (EndMT) has been demonstrated to be involved in pulmonary vascular remodeling. It is partly attributed to oxidative and inflammatory stresses in endothelial cells. In current study, we conducted a series of experiments to clarify the effect of salvianolic acid A (SAA), a kind of polyphenol compound, in the process of EndMT in human pulmonary arterial endothelial cells and in vivo therapeutic efficacy on vascular remodeling in monocrotaline (MCT)-induced EndMT. EndMT was induced by TGFβ1 in human pulmonary arterial endothelial cells (HPAECs). SAA significantly attenuated EndMT, simultaneously inhibited cell migration and reactive oxygen species (ROS) formation. In MCT-induced pulmonary arterial hypertension (PAH) model, SAA improved vascular function, decreased TGFβ1 level and inhibited inflammation. Mechanistically, SAA stimulated Nrf2 translocation and subsequent heme oxygenase-1 (HO-1) up-regulation. The effect of SAA on EndMT in vitro was abolished by ZnPP, a HO-1 inhibitor. In conclusion, this study indicates a deleterious impact of oxidative stress on EndMT. Polyphenol antioxidant treatment may provide an adjunctive action to alleviate pulmonary vascular remodeling via inhibiting EndMT.
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