title: Protective effects of hydrogen sulfide against angiotensin II-induced endoplasmic reticulum stress in HUVECs.
abstract: The inhibitory effects of hydrogen sulfide (H2S) on angiotensin II (AngII)-stimulated human umbilical vein endothelial cell (HUVEC) dysfunction remain to be elucidated. Endoplasmic reticulum (ER) stress has been detected in endothelial dysfunction (ED). The present study aimed to determine whether H2S may exert an inhibitory effect on AngII‑induced ER stress. Using HUVECs as a model system, the present study used western blotting to detect protein expression, intracellular reactive oxygen species (ROS) levels were determined by oxidative conversion of cell permeable DCFH‑DA to fluorescent dichlorofluorescein, CCK‑8 assay was used to investigate the cell viability, methylene blue was used to investigate the CSE activity, TUNEL was used to investigate the cells apoptosis. The present study demonstrated that AngII not only upregulated the expression levels of inducible nitric oxide synthase (iNOS), stimulated ROS production and increased cell apoptosis, but also downregulated the expression levels of phosphorylated‑endothelial nitric oxide synthase, decreased the expression and activity of cystathionine‑c‑lyase (CSE) and decreased cell viability. Furthermore, hydrogen peroxide (H2O2; an exogenous ROS) downregulated the expression and activity of CSE, and had similar effects as AngII, whereas the inhibitory effects of AngII were completely suppressed by N-acetyl-L-cysteine (a ROS scavenger). In addition, AngII induced the expression of glucose‑regulated protein 78 (GRPP78) and C/EBP homologous protein (CHOP), which are markers of ER stress. Conversely, the stimulatory effects of AngII were completely inhibited by sodium hydrosulfide (NaHS; a H2S donor). Treatment with NaHS attenuated ROS production, inhibited CHOP and GRP78 expression, and decreased cell apoptosis. The present study indicated that AngII induced ED via the activation of ER stress in HUVECs. In addition, the effects of AngII on ER stress could be suppressed by H2S.
authors.affiliation: Department of Cardiology/Cardiac Catheterisation Lab, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Heng-Jing
authors.initials: HJ
authors.lastname: Hu
authors.affiliation: Institute of Cardiovascular Disease and Key Lab For Arteriosclerology of Hunan, University of South China, Hengyang, Hunan 421001, P.R. China.
authors.forename: Zhi-Sheng
authors.initials: ZS
authors.lastname: Jiang
authors.affiliation: Department of Cardiology/Cardiac Catheterisation Lab, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Qiu
authors.affiliation: Department of Cardiology/Cardiac Catheterisation Lab, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Sheng-Hua
authors.initials: SH
authors.lastname: Zhou
authors.affiliation: Department of Cardiology/Cardiac Catheterisation Lab, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Qi-Ming
authors.initials: QM
authors.lastname: Liu
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D020011:Protective Agents; D017382:Reactive Oxygen Species; D000804:Angiotensin II; D052247:Nitric Oxide Synthase Type II; D006862:Hydrogen Sulfide