title: Adiporedoxin suppresses endothelial activation via inhibiting MAPK and NF-κB signaling.
abstract: Adiporedoxin (Adrx) is a recently discovered redox regulatory protein that is preferentially expressed in adipose tissue and plays a critical role in the regulation of metabolism via its modulation of adipocyte protein secretion. We here report that Adrx suppresses endothelial cell activation via inhibiting MAPK and NF-kB signaling pathways. Adrx is constitutively expressed in human vascular endothelial cells, and significantly induced by a variety of stimuli such as TNFα, IL-1β, H2O2and OxLDL. Overexpression of Adrx significantly attenuated TNFα-induced expression of VCAM-1 and ICAM-1, and thus reduced monocyte adherence to human umbilical vein endothelial cells (HUVECs). Conversely, siRNA-mediated knockdown of Adrx increased TNFα-induced expression of adhesion molecules and monocyte adherence to HUVECs. Furthermore, forced expression of Adrx decreased TNFα-induced activation of ERK1/2, JNK, p38 and IKKs in HUVECs. Adrx mutant in the CXXC motif that lost its anti-redox activity is less efficient than the wild-type Adrx, suggesting that Adrx-mediated inhibition of endothelial activation is partially dependent on its antioxidant activity. Finally, Adrx expression was markedly increased in human atheroma compared with normal tissue from the same carotid arteries. These results suggest that Adrx is an endogenous inhibitor of endothelial activation, and might be a therapeutic target for vascular inflammatory diseases.
authors.affiliation: Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, China.|Department of Basic Medical Science, Shock/Trauma Research Center, School of Medicine, University of Missouri Kansas City, Kansas City, MO 64108, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: He
authors.affiliation: Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Guo
authors.affiliation: Department of Basic Medical Science, Shock/Trauma Research Center, School of Medicine, University of Missouri Kansas City, Kansas City, MO 64108, USA.|Institute of Translational Medicine, Nanchang University, Nanchang, Jiangxi, 330031, P. R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC 29209, USA.
authors.forename: Fatma
authors.initials: F
authors.lastname: Saaoud
authors.affiliation: Department of Basic Medical Science, Shock/Trauma Research Center, School of Medicine, University of Missouri Kansas City, Kansas City, MO 64108, USA.
authors.forename: Brooks D
authors.initials: BD
authors.lastname: Kimmis
authors.affiliation: Department of Basic Medical Science, Shock/Trauma Research Center, School of Medicine, University of Missouri Kansas City, Kansas City, MO 64108, USA.
authors.forename: Jeena
authors.initials: J
authors.lastname: Sandhu
authors.affiliation: Department of Basic Medical Science, Shock/Trauma Research Center, School of Medicine, University of Missouri Kansas City, Kansas City, MO 64108, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Fan
authors.affiliation: Department of Obstetrics and Gynecology, University of Missouri - Kansas City School of Medicine, Kansas City, MO 64108, USA.
authors.forename: Dev
authors.initials: D
authors.lastname: Maulik
authors.affiliation: Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC 29209, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Lessner
authors.affiliation: Department of Basic Medical Science, Shock/Trauma Research Center, School of Medicine, University of Missouri Kansas City, Kansas City, MO 64108, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Papasian
authors.affiliation: Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC 29209, USA.
authors.forename: Daping
authors.initials: D
authors.lastname: Fan
authors.affiliation: Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, China.
authors.forename: Zhisheng
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Department of Basic Medical Science, Shock/Trauma Research Center, School of Medicine, University of Missouri Kansas City, Kansas City, MO 64108, USA.
authors.forename: Mingui
authors.initials: M
authors.lastname: Fu
mesh_terms: D001158:Arteries / Q000378:metabolism; D002448:Cell Adhesion; D002460:Cell Line; D042783:Endothelial Cells / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D020935:MAP Kinase Signaling System; D009000:Monocytes / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D054464:Peroxiredoxins; D058226:Plaque, Atherosclerotic / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D016328:NF-kappa B; C555781:PRXL2A protein, human; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D054464:Peroxiredoxins