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Oxidative Medicine and Cellular Longevity
Volume 2017 (2017), Article ID 5736506, 13 pages
Research Article

Homocysteine Induces Apoptosis of Human Umbilical Vein Endothelial Cells via Mitochondrial Dysfunction and Endoplasmic Reticulum Stress

1Department of Cardiology, Tangdu Hospital of the Fourth Military Medical University, Xi’an, China
2Department of Cardiology, Xian Yang Central Hospital, Xi’an, China
3Department of Cardiology, Shaanxi Provincial Chinese Traditional Medicine Hospital, Xi’an, China
4Department of Pharmacy, Tangdu Hospital of the Fourth Military Medical University, Xi’an, China

Correspondence should be addressed to Lianyou Zhao

Received 12 December 2016; Revised 16 February 2017; Accepted 16 March 2017; Published 28 May 2017

Academic Editor: Igor A. Sobenin

Copyright © 2017 Zhimin Zhang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Homocysteine- (Hcy-) induced endothelial cell apoptosis has been suggested as a cause of Hcy-dependent vascular injury, while the proposed molecular pathways underlying this process are unclear. In this study, we investigated the adverse effects of Hcy on human umbilical vein endothelial cells (HUVEC) and the underlying mechanisms. Our results demonstrated that moderate-dose Hcy treatment induced HUVEC apoptosis in a time-dependent manner. Furthermore, prolonged Hcy treatment increased the expression of NOX4 and the production of intracellular ROS but decreased the ratio of Bcl-2/Bax and mitochondrial membrane potential (MMP), resulting in the leakage of cytochrome c and activation of caspase-3. Prolonged Hcy treatment also upregulated glucose-regulated protein 78 (GRP78), activated protein kinase RNA-like ER kinase (PERK), and induced the expression of C/EBP homologous protein (CHOP) and the phosphorylation of NF-κb. The inhibition of NOX4 decreased the production of ROS and alleviated the Hcy-induced HUVEC apoptosis and ER stress. Blocking the PERK pathway partly alleviated Hcy-induced HUVEC apoptosis and the activation of NF-κb. Taken together, our results suggest that Hcy-induced mitochondrial dysfunction crucially modulated apoptosis and contributed to the activation of ER stress in HUVEC. The excessive activation of the PERK pathway partly contributed to Hcy-induced HUVEC apoptosis and the phosphorylation of NF-κb.