title: Oxidized lipoprotein(a) increases endothelial cell monolayer permeability via ROS generation.
abstract: Oxidized lipoprotein(a) (oxLp(a)) is a more potent marker of atherogenesis than native Lp(a). However, the molecular mechanisms of oxLp(a) activity are not clear. Reactive oxygen species (ROS) have recently been suggested as acting as intracellular second messengers. In this study, the effects of oxLp(a) on endothelial cell monolayer permeability and the role of reactive oxygen species (ROS) generation in these effects were investigated. Our results showed that oxLp(a) inhibited desmoglein-1 (DSG1) and desmocollin-2 (DSC2) expression at both mRNA and protein levels in a dose- and time-dependent manner, and increased the generation of cellular ROS. Down-regulation of DSG1 and DSC2 was strengthened by pretreatment with H₂O₂ and attenuated by superoxide dismutase (SOD) treatment. Furthermore, oxLp(a) increased endothelial cell monolayer permeability, and this effect was enhanced by H₂O₂ and blunted by SOD. Taken together, these results demonstrate that oxLp(a) increases endothelial cell monolayer permeability, which is mediated at least in part via ROS generation.
authors.affiliation: Key Laboratory for Arteriosclerology of Hunan Province, Institute of Cardiovascular Disease, University of South China, Hengyang 421001, China.
authors.forename: Deng-heng
authors.initials: DH
authors.lastname: Wei
authors.forename: Xiao-lei
authors.initials: XL
authors.lastname: Zhang
authors.forename: Ren
authors.initials: R
authors.lastname: Wang
authors.forename: Jun-fa
authors.initials: JF
authors.lastname: Zeng
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.forename: Shuang
authors.initials: S
authors.lastname: Li
authors.forename: Xiao-long
authors.initials: XL
authors.lastname: Lin
authors.forename: Zhi-sheng
authors.initials: ZS
authors.lastname: Jiang
authors.forename: Gui-xue
authors.initials: GX
authors.lastname: Wang
authors.forename: Zuo
authors.initials: Z
authors.lastname: Wang
mesh_terms: D051187:Desmocollins / Q000235:genetics / Q000378:metabolism; D051183:Desmoglein 1 / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism*; D005786:Gene Expression Regulation; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D015227:Lipid Peroxidation; D017270:Lipoprotein(a) / Q000378:metabolism*; D010084:Oxidation-Reduction; D010539:Permeability; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: C081561:DSC2 protein, human; C495297:DSG1 protein, human; D051187:Desmocollins; D051183:Desmoglein 1; D017270:Lipoprotein(a); D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase