title: Critical role of vascular peroxidase 1 in regulating endothelial nitric oxide synthase.
abstract: Vascular peroxidase 1 (VPO1) is a member of the peroxidase family which aggravates oxidative stress by producing hypochlorous acid (HOCl). Our previous study demonstrated that VPO1 plays a critical role in endothelial dysfunction through dimethylarginine dimethylaminohydrolase2 (DDAH2)/asymmetric Dimethylarginine (ADMA) pathway. Hereby we describe the regulatory role of VPO1 on endothelial nitric oxide synthase (eNOS) expression and activity in human umbilical vein endothelial cells (HUVECs). In HUVECs AngiotensinII (100nM) treatment reduced Nitric Oxide (NO) production, decreased eNOS expression and activity, which were reversed by VPO1 siRNA. Knockdown of VPO1 also attenuated ADMA production and eNOS uncoupling while enhancing phosphorylated ser1177 eNOS expression level. Furthermore, HOCl stimulation was shown to directly induce ADMA production and eNOS uncoupling, decrease phosphorylated ser1177 eNOS expression. It also significantly suppressed eNOS expression and activity together with NO production. Therefore, VPO1 plays a vital role in regulating eNOS expression and activity via hydrogen peroxide (H2O2)-VPO1-HOCl pathway.
authors.affiliation: Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Zhaoya
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Yanbo
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Peng
authors.affiliation: Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Yixin
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Tianlun
authors.initials: T
authors.lastname: Yang
authors.affiliation: Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Zaixin
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Division of Pulmonary, Allergy & Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Guangjie
authors.initials: G
authors.lastname: Cheng
authors.affiliation: Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha 410008, China. Electronic address: xyzgg2006@sina.com.
authors.forename: Guogang
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha 410008, China. Electronic address: xyshiruizheng@csu.edu.cn.
authors.forename: Ruizheng
authors.initials: R
authors.lastname: Shi
mesh_terms: D000581:Amidohydrolases / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D055785:Gene Knockdown Techniques; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000737:chemistry / Q000378:metabolism*; D010544:Peroxidases / Q000235:genetics* / Q000378:metabolism*; D010766:Phosphorylation; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000097423:Peroxidasin
chemical_list: D000581:Amidohydrolases; D000804:Angiotensin II; D006861:Hydrogen Peroxide; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D010544:Peroxidases; D012694:Serine; C535215:PXDN protein, human; D000097423:Peroxidasin; C496314:NOS3 protein, human; C059999:dimethylargininase
keywords: Angiotensin II; Asymmetricdimethylarginine; Endothelial nitric oxide synthase; Nitric oxide; Oxidative stress; Vascular peroxidase 1