PMID- 27190988 OWN - NLM STAT- MEDLINE DCOM- 20170213 LR - 20181113 IS - 2314-6141 (Electronic) IS - 2314-6133 (Print) VI - 2016 DP - 2016 TI - HSP27 Inhibits Homocysteine-Induced Endothelial Apoptosis by Modulation of ROS Production and Mitochondrial Caspase-Dependent Apoptotic Pathway. PG - 4847874 LID - 10.1155/2016/4847874 [doi] LID - 4847874 AB - 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. FAU - Tian, Xin AU - Tian X AD - Department of Cardiology, The Second Hospital of Jilin University, 218 Ziqiang Street, Changchun 130041, China. FAU - Zhao, Lei AU - Zhao L AD - Department of Cardiology, The Second Hospital of Jilin University, 218 Ziqiang Street, Changchun 130041, China. FAU - Song, Xianjing AU - Song X AD - Department of Cardiology, The Second Hospital of Jilin University, 218 Ziqiang Street, Changchun 130041, China. FAU - Yan, Youyou AU - Yan Y AD - Department of Cardiology, The Second Hospital of Jilin University, 218 Ziqiang Street, Changchun 130041, China. FAU - Liu, Ning AU - Liu N AD - Department of Cardiology, The Second Hospital of Jilin University, 218 Ziqiang Street, Changchun 130041, China. FAU - Li, Tianyi AU - Li T AD - Department of Cardiology, The Second Hospital of Jilin University, 218 Ziqiang Street, Changchun 130041, China. FAU - Yan, Bingdi AU - Yan B AD - Department of Respiratory Medicine, The Second Hospital of Jilin University, 218 Ziqiang Street, Changchun 130041, China. FAU - Liu, Bin AU - Liu B AUID- ORCID: 0000-0003-2017-2160 AD - Department of Cardiology, The Second Hospital of Jilin University, 218 Ziqiang Street, Changchun 130041, China. LA - eng PT - Journal Article DEP - 20160417 PL - United States TA - Biomed Res Int JT - BioMed research international JID - 101600173 RN - 0 (HSP27 Heat-Shock Proteins) RN - 0 (Protective Agents) RN - 0 (Reactive Oxygen Species) RN - 0LVT1QZ0BA (Homocysteine) RN - 31C4KY9ESH (Nitric Oxide) RN - EC 3.4.22.- (Caspases) SB - IM MH - Apoptosis/*drug effects MH - Caspases/*metabolism MH - HSP27 Heat-Shock Proteins/*metabolism MH - Homocysteine/*pharmacology MH - Human Umbilical Vein Endothelial Cells/cytology/drug effects/metabolism MH - Humans MH - Membrane Potential, Mitochondrial/drug effects MH - Mitochondria/drug effects/metabolism MH - Nitric Oxide/biosynthesis MH - Protective Agents/pharmacology MH - Reactive Oxygen Species/*metabolism MH - Signal Transduction/*drug effects PMC - PMC4852127 EDAT- 2016/05/18 06:00 MHDA- 2017/02/14 06:00 PMCR- 2016/04/17 CRDT- 2016/05/19 06:00 PHST- 2016/01/13 00:00 [received] PHST- 2016/03/18 00:00 [revised] PHST- 2016/03/23 00:00 [accepted] PHST- 2016/05/19 06:00 [entrez] PHST- 2016/05/18 06:00 [pubmed] PHST- 2017/02/14 06:00 [medline] PHST- 2016/04/17 00:00 [pmc-release] AID - 10.1155/2016/4847874 [doi] PST - ppublish SO - Biomed Res Int. 2016;2016:4847874. doi: 10.1155/2016/4847874. Epub 2016 Apr 17.