title: Involvement of vascular peroxidase 1 in angiotensin II-induced vascular smooth muscle cell proliferation.
abstract: OBJECTIVE
  Vascular peroxidase 1 (VPO1) is a newly identified haem-containing peroxidase that catalyses the oxidation of a variety of substrates by hydrogen peroxide (H(2)O(2)). Considering the well-defined effects of H(2)O(2) on the vascular remodelling during hypertension, and that VPO1 can utilize H(2)O(2) generated from co-expressed NADPH oxidases to catalyse peroxidative reactions, the aims of this study were to determine the potential role of VPO1 in vascular remodelling during hypertension.
  
  
  RESULTS
  The vascular morphology and the expression of VPO1 in arterial tissues of spontaneously hypertensive rats and Wistar-Kyoto rats were assessed. The VPO1 expression was significantly increased concomitantly with definite vascular remodelling assessed by evaluating the media thickness, lumen diameter, media thickness-to-lumen diameter ratio and mean nuclear area in artery media in spontaneously hypertensive rats. In addition, in cultured rat aortic smooth muscle cells we found that the angiotensin II-mediated cell proliferation was inhibited by knockdown of VPO1 using small hairpin RNA. Moreover, the NADPH oxidase inhibitor, apocynin, and the hydrogen peroxide scavenger, catalase, but not the ERK1/2 inhibitor, PD98059, attenuated angiotensin II-mediated up-regulation of VPO1 and generation of hypochlorous acid.
  
  
  CONCLUSIONS
  VPO1 is a novel regulator of vascular smooth muscle cell proliferation via NADPH oxidase-H(2)O(2)-VPO1-hypochlorous acid-ERK1/2 pathways, which may contribute to vascular remodelling in hypertension.
authors.affiliation: Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Ruizheng
authors.initials: R
authors.lastname: Shi
authors.forename: Changping
authors.initials: C
authors.lastname: Hu
authors.forename: Qiong
authors.initials: Q
authors.lastname: Yuan
authors.forename: Tianlun
authors.initials: T
authors.lastname: Yang
authors.forename: Jun
authors.initials: J
authors.lastname: Peng
authors.forename: Yuanjian
authors.initials: Y
authors.lastname: Li
authors.forename: Yongping
authors.initials: Y
authors.lastname: Bai
authors.forename: Zehong
authors.initials: Z
authors.lastname: Cao
authors.forename: Guangjie
authors.initials: G
authors.lastname: Cheng
authors.forename: Guogang
authors.initials: G
authors.lastname: Zhang
mesh_terms: D000704:Analysis of Variance; D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D001013:Aorta, Thoracic / Q000201:enzymology / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D016166:Free Radical Scavengers / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism; D006973:Hypertension / Q000201:enzymology* / Q000473:pathology; D006997:Hypochlorous Acid / Q000378:metabolism; D008297:Male; D008638:Mesenteric Arteries / Q000201:enzymology / Q000473:pathology; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009195:Peroxidase / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D015398:Signal Transduction; D013997:Time Factors; D000097423:Peroxidasin
chemical_list: D000804:Angiotensin II; D004791:Enzyme Inhibitors; D016326:Extracellular Matrix Proteins; D016166:Free Radical Scavengers; D006861:Hydrogen Peroxide; D006997:Hypochlorous Acid; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D019255:NADPH Oxidases; D009195:Peroxidase; D012333:RNA, Messenger; D000097423:Peroxidasin