Homocysteine causes vascular endothelial dysfunction by disrupting endoplasmic reticulum redox homeostasis.

ABSTRACT: 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 peroxid

SUBMITTER: Wu X 

PROVIDER: S-EPMC6174864 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature