Homocysteine causes vascular endothelial dysfunction by disrupting endoplasmic reticulum redox homeostasis.
Homocysteine causes vascular endothelial dysfunction by disrupting endoplasmic reticulum redox homeostasis.
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同型半胱氨酸通过破坏内质网氧化还原稳态导致血管内皮功能障碍
DOI：
10.1016/j.redox.2018.09.021
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发表时间：
2019-01
期刊：
影响因子：
11.4
通讯作者：
Wang L
中科院分区：
文献类型：
--
作者：
Wu X;Zhang L;Miao Y;Yang J;Wang X;Wang CC;Feng J;Wang L
Endothelial dysfunction induced by hyperhomocysteinemia (HHcy) plays a critical role in vascular pathology. However, little is known about the role of endoplasmic reticulum (ER) redox homeostasis in HHcy-induced endothelial dysfunction. Here, we show that Hcy induces ER oxidoreductin-1α (Ero1α) expression with ER stress and inflammation in human umbilical vein endothelial cells and in the arteries of HHcy mice. Hcy upregulates Ero1α expression by promoting binding of hypoxia-inducible factor 1α to the ERO1A promoter. Notably, Hcy rather than other thiol agents markedly increases the GSH/GSSG ratio in the ER, therefore allosterically activating Ero1α to produce H2O2 and trigger ER oxidative stress. By contrast, the antioxidant pathway mediated by ER glutathione peroxidase 7 (GPx7) is downregulated in HHcy mice. Ero1α knockdown and GPx7 overexpression protect the endothelium from HHcy-induced ER oxidative stress and inflammation. Our work suggests that targeting ER redox homeostasis could be used as an intervention for HHcy-related vascular diseases.
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影响因子：
82.9
作者：
通讯作者：
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影响因子：
21.3
作者：
通讯作者：
--
影响因子：
14.8
作者：
Dahl, John Arne;Collas, Philippe
通讯作者：
Collas, Philippe
影响因子：
11.4
作者：
Benham, AM;Cabibbo, A;Braakman, I
通讯作者：
Braakman, I
影响因子：
4
作者：
Eletto, Davide;Chevet, Eric;Appenzeller-Herzog, Christian
通讯作者：
Appenzeller-Herzog, Christian