PMID- 26142204 OWN - NLM STAT- MEDLINE DCOM- 20160503 LR - 20150804 IS - 1874-1754 (Electronic) IS - 0167-5273 (Linking) VI - 197 DP - 2015 Oct 15 TI - Role of vascular peroxidase 1 in senescence of endothelial cells in diabetes rats. PG - 182-91 LID - S0167-5273(15)30035-8 [pii] LID - 10.1016/j.ijcard.2015.06.098 [doi] AB - BACKGROUND: Reactive oxygen species (ROS) is thought as a major reason of vascular injury in diabetes. Vascular peroxidase 1 (VPO1) is a newly found peroxidase playing an important role in inducing oxidative stress. In the present experiment, we tested the role of VPO1 in senescence of endothelial cells in streptozotocin (STZ)-induced diabetic rats and cultured endothelial cells. METHODS: Blood samples were collected from carotid arteries. Vasodilator responses to acetylcholine (Ach) in the isolated aortic rings were measured, serum concentration of glucose, tumor necrosis factor-alpha (TNF-alpha) and monocyte chemoattractant protein-1 (MCP-1) and the expression of VPO1 in the aorta were determined. Endothelial cells were treated with high glucose or H2O2, the concentrations of MCP-1, TNF-alpha and hypochlorous acid (HOCl) and the expression of VPO1 were determined. shRNA of VPO1 was used for mechanism research in cultured cells. RESULTS: Vasodilator responses to Ach were impaired markedly and the serum concentrations of glucose, TNF-alpha and MCP-1 were significantly increased in diabetic rats. The expression of VPO1 in the aorta was upregulated in diabetic rats. High glucose treatment significantly decreased cell viability and elevated the levels of MCP-1, TNF-alpha and HOCl and upregulated the expression of VPO1. H2O2 treatment significantly induced cellular senescence, inhibited eNOS expression and NO production. The effects of high glucose and H2O2 were attenuated by shRNA interference of VPO1. CONCLUSIONS: VPO1 plays an important role in senescence of endothelial cells and endothelial dysfunction by induction of oxidative stress and inflammatory reaction in type 2 diabetic rats. CI - Copyright (c) 2015 Elsevier Ireland Ltd. All rights reserved. FAU - Liu, Si-Yu AU - Liu SY AD - Department of Pharmacology, School of Pharmaceutical Science, Central South University, Changsha 410078, China; Department of Pharmacology, Xiangnan College, Chenzhou 423000, China. FAU - Yuan, Qiong AU - Yuan Q AD - Department of Pharmacology, School of Pharmaceutical Science, Central South University, Changsha 410078, China; Department of Pharmacology, Medical College, Wuhan University of Science and Technology, Wuhan 430081, China. FAU - Li, Xiao-Hui AU - Li XH AD - Department of Pharmacology, School of Pharmaceutical Science, Central South University, Changsha 410078, China. FAU - Hu, Chang-Ping AU - Hu CP AD - Department of Pharmacology, School of Pharmaceutical Science, Central South University, Changsha 410078, China. FAU - Hu, Rong AU - Hu R AD - Department of Pharmacology, School of Pharmaceutical Science, Central South University, Changsha 410078, China. FAU - Zhang, Guo-Gang AU - Zhang GG AD - Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha 410078, China. FAU - Li, Dai AU - Li D AD - Department of Pharmacology, School of Pharmaceutical Science, Central South University, Changsha 410078, China. FAU - Li, Yuan-Jian AU - Li YJ AD - Department of Pharmacology, School of Pharmaceutical Science, Central South University, Changsha 410078, China. Electronic address: yuan_jianli@yahoo.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150627 PL - Netherlands TA - Int J Cardiol JT - International journal of cardiology JID - 8200291 RN - 0 (Hemeproteins) RN - 0 (RNA, Messenger) RN - EC 1.11.1- (vascular peroxidase, rat) RN - EC 1.11.1.- (Peroxidases) SB - IM MH - Animals MH - Blotting, Western MH - Diabetes Mellitus, Experimental/enzymology/*genetics/physiopathology MH - Diabetes Mellitus, Type 2/enzymology/genetics/physiopathology MH - Endothelium, Vascular/*enzymology/physiopathology MH - *Gene Expression Regulation MH - Hemeproteins/biosynthesis/*genetics MH - Humans MH - Male MH - *Oxidative Stress MH - Peroxidases/biosynthesis/*genetics MH - RNA, Messenger/*genetics MH - Rats MH - Rats, Sprague-Dawley MH - Real-Time Polymerase Chain Reaction MH - *Vasodilation OTO - NOTNLM OT - Endothelial cells OT - Senescence OT - Type 2 diabetes mellitus OT - Vascular peroxidase EDAT- 2015/07/05 06:00 MHDA- 2016/05/04 06:00 CRDT- 2015/07/05 06:00 PHST- 2015/01/25 00:00 [received] PHST- 2015/06/06 00:00 [revised] PHST- 2015/06/23 00:00 [accepted] PHST- 2015/07/05 06:00 [entrez] PHST- 2015/07/05 06:00 [pubmed] PHST- 2016/05/04 06:00 [medline] AID - S0167-5273(15)30035-8 [pii] AID - 10.1016/j.ijcard.2015.06.098 [doi] PST - ppublish SO - Int J Cardiol. 2015 Oct 15;197:182-91. doi: 10.1016/j.ijcard.2015.06.098. Epub 2015 Jun 27.