title: LOX‑1 is implicated in oxidized low‑density lipoprotein‑induced oxidative stress of macrophages in atherosclerosis.
abstract: Induction of oxidative stress has a causal role in atherosclerosis. The aim of the present study was to examine the role of lectin‑like oxidized low‑density lipoprotein receptor‑1 (LOX‑1) in oxidized low‑density lipoprotein (OxLDL)‑induced oxidative stress in atherosclerosis. Small interfering RNA (siRNA) technology was employed to decrease the expression of LOX‑1 in mouse RAW264.7 macrophages and the effects of LOX‑1 silencing on OxLDL‑induced reactive oxygen species (ROS) generation and NADPH oxidase (NOX) expression were investigated. The in vivo effects of reducing LOX‑1 were also examined in a mouse model (ApoE‑/‑) of high‑fat diet‑induced atherosclerosis. Compared with the control cells, OxLDL exposure led to a significant (P<0.05) increase in the intracellular levels of malondialdehyde and ROS and a significant decrease in the activity of superoxide dismutase. Delivery of LOX‑1‑targeting siRNA significantly (P<0.05) reversed the alterations in oxidative stress parameters induced by OxLDL. LOX‑1 silencing downregulated the expression of NOX2, Rac1, p47phox and p22phox and impaired the activation of mitogen‑activated protein kinases in OxLDL‑treated cells. Adenoviral delivery of LOX‑1 siRNA caused a significant increase in the size of the fibrous cap and a decrease in the macrophage content in lesions, compared with the control mice. Western blot analysis demonstrated that the protein expression levels of NOX1, Rac1, p47phox and p22phox in aortic lesions were significantly lower in the LOX‑1 siRNA group than in the control group. LOX‑1 is implicated in OxLDL‑induced oxidative stress of macrophages in atherosclerosis, which in part, involves the regulation of NADPH oxidases.
authors.affiliation: Department of Cardiology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
authors.forename: Hui-Yu
authors.initials: HY
authors.lastname: Yang
authors.affiliation: Department of Cardiology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
authors.forename: Yun-Fei
authors.initials: YF
authors.lastname: Bian
authors.affiliation: The Scientific Research Laboratory Center, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
authors.forename: Hua-Ping
authors.initials: HP
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
authors.forename: Fen
authors.initials: F
authors.lastname: Gao
authors.affiliation: Department of Cardiology, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
authors.forename: Chuan-Shi
authors.initials: CS
authors.lastname: Xiao
authors.affiliation: Department of Cardiology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liang
authors.affiliation: Department of Cardiology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Cardiology, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
authors.forename: Na-Na
authors.initials: NN
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Yang
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002460:Cell Line; D003573:Cytochrome b Group / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D020868:Gene Silencing; D008055:Lipids / Q000097:blood; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D058226:Plaque, Atherosclerotic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D051127:Scavenger Receptors, Class E / Q000235:genetics / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D003573:Cytochrome b Group; D008055:Lipids; D008077:Lipoproteins, LDL; D008562:Membrane Glycoproteins; C495138:Olr1 protein, mouse; D034741:RNA, Small Interfering; D051127:Scavenger Receptors, Class E; C099252:oxidized low density lipoprotein; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C515614:Cyba protein, mouse; C060505:neutrophil cytosolic factor 1; D020830:rac1 GTP-Binding Protein