title: PCSK9 siRNA suppresses the inflammatory response induced by oxLDL through             inhibition of NF-κB activation in THP-1-derived macrophages.
abstract: Proprotein convertase subtilisin/kexin 9 (PCSK9), a member of the protein-converting             enzyme family, is highly expressed in adult hepatocytes and small intestinal enterocytes.             To our knowledge, in this study, we demonstrate for the first time that PCSK9             is upregulated in a dose-dependent manner via oxidized low-density lipoprotein             (oxLDL) stimulation in THP-1-derived macrophages. PCSK9 small interfering RNA             (siRNA) suppresses the oxLDL-induced inflammatory cytokine expression in THP-1-derived             macrophages. The exposure of macrophages to oxLDL markedly increased the expression             of NF-κB protein in the nucleus. However, this effect was significantly attenuated             by PCSK9 siRNA. These findings indicate that PCSK9 expression is induced by oxLDL,             and that PCSK9 siRNA protects against inflammation via the inhibition of NF-κB             activation in oxLDL-stimulated THP-1-derived macrophages. Our results suggest             that PCSK9 may be used as a therapeutic target for the treatment of atherosclerosis             since PCSK9 siRNA suppresses oxLDL-induced IκB-α degradation and NF-κB nuclear             translocation into THP-1-derived macrophages.
authors: Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, PR China.
authors: Zhihan
authors: Z
authors: Tang
authors: Lu
authors: L
authors: Jiang
authors: Juan
authors: J
authors: Peng
authors: Zhong
authors: Z
authors: Ren
authors: Dangheng
authors: D
authors: Wei
authors: Chunyang
authors: C
authors: Wu
authors: Lihong
authors: L
authors: Pan
authors: Zhisheng
authors: Z
authors: Jiang
authors: Lushan
authors: L
authors: Liu
mesh_terms: D002460:Cell Line; D006801:Humans; D008077:Lipoproteins, LDL / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D016328:NF-kappa B / Q000276:immunology*; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000235:genetics* / Q000276:immunology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D012697:Serine Endopeptidases / Q000235:genetics* / Q000276:immunology*; D015854:Up-Regulation
chemical_list: D008077:Lipoproteins, LDL; D016328:NF-kappa B; D034741:RNA, Small Interfering; C099252:oxidized low density lipoprotein; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases