title: Role of vascular peroxidase 1 in senescence of endothelial cells in diabetes rats.
abstract: 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-α (TNF-α) 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-α 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-α 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-α 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.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Science, Central South University, Changsha 410078, China; Department of Pharmacology, Xiangnan College, Chenzhou 423000, China.
authors.forename: Si-Yu
authors.initials: SY
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Science, Central South University, Changsha 410078, China.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Li
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Science, Central South University, Changsha 410078, China.
authors.forename: Chang-Ping
authors.initials: CP
authors.lastname: Hu
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Science, Central South University, Changsha 410078, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Hu
authors.affiliation: Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha 410078, China.
authors.forename: Guo-Gang
authors.initials: GG
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Science, Central South University, Changsha 410078, China.
authors.forename: Dai
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Science, Central South University, Changsha 410078, China. Electronic address: yuan_jianli@yahoo.com.
authors.forename: Yuan-Jian
authors.initials: YJ
authors.lastname: Li
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000201:enzymology* / Q000503:physiopathology; D005786:Gene Expression Regulation; D006420:Hemeproteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D008297:Male; D018384:Oxidative Stress; D010544:Peroxidases / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D014664:Vasodilation
chemical_list: D006420:Hemeproteins; D012333:RNA, Messenger; C573339:vascular peroxidase, rat; D010544:Peroxidases
keywords: Endothelial cells; Senescence; Type 2 diabetes mellitus; Vascular peroxidase