title: HSP27 Inhibits Homocysteine-Induced Endothelial Apoptosis by Modulation of ROS Production and Mitochondrial Caspase-Dependent Apoptotic Pathway.
abstract: Objectives. Elevated plasma homocysteine (Hcy) could lead to endothelial dysfunction and is viewed as an independent risk factor for atherosclerosis. Heat shock protein 27 (HSP27), a small heat shock protein, is reported to exert protective effect against atherosclerosis. This study aims to investigate the protective effect of HSP27 against Hcy-induced endothelial cell apoptosis in human umbilical vein endothelial cells (HUVECs) and to determine the underlying mechanisms. Methods. Apoptosis, reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) of normal or HSP27-overexpressing HUVECs in the presence of Hcy were analyzed by flow cytometry. The mRNA and protein expression levels were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Results. We found that Hcy could induce cell apoptosis with corresponding decrease of nitric oxide (NO) level, increase of endothelin-1 (ET-1), intracellular adhesion molecule-1 (ICAM-1), vascular cellular adhesion molecule-1 (VCAM-1), and monocyte chemoattractant protein-1 (MCP-1) levels, elevation of ROS, and dissipation of MMP. In addition, HSP27 could protect the cell against Hcy-induced apoptosis and inhibit the effect of Hcy on HUVECs. Furthermore, HSP27 could increase the ratio of Bcl-2/Bax and inhibit caspase-3 activity. Conclusions. Therefore, we concluded that HSP27 played a protective role against Hcy-induced endothelial apoptosis through modulation of ROS production and the mitochondrial caspase-dependent apoptotic pathway.
authors.affiliation: Department of Cardiology, The Second Hospital of Jilin University, 218 Ziqiang Street, Changchun 130041, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Tian
authors.affiliation: Department of Cardiology, The Second Hospital of Jilin University, 218 Ziqiang Street, Changchun 130041, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, The Second Hospital of Jilin University, 218 Ziqiang Street, Changchun 130041, China.
authors.forename: Xianjing
authors.initials: X
authors.lastname: Song
authors.affiliation: Department of Cardiology, The Second Hospital of Jilin University, 218 Ziqiang Street, Changchun 130041, China.
authors.forename: Youyou
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Department of Cardiology, The Second Hospital of Jilin University, 218 Ziqiang Street, Changchun 130041, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.affiliation: Department of Cardiology, The Second Hospital of Jilin University, 218 Ziqiang Street, Changchun 130041, China.
authors.forename: Tianyi
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, The Second Hospital of Jilin University, 218 Ziqiang Street, Changchun 130041, China.
authors.forename: Bingdi
authors.initials: B
authors.lastname: Yan
authors.affiliation: Department of Cardiology, The Second Hospital of Jilin University, 218 Ziqiang Street, Changchun 130041, China.
authors.forename: Bin
authors.identifier: 0000-0003-2017-2160
authors.initials: B
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism*; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism*; D006710:Homocysteine / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D020011:Protective Agents / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D055551:HSP27 Heat-Shock Proteins; D020011:Protective Agents; D017382:Reactive Oxygen Species; D006710:Homocysteine; D009569:Nitric Oxide; D020169:Caspases