title: Salusin-β induces foam cell formation and monocyte adhesion in human vascular smooth muscle cells via miR155/NOX2/NFκB pathway.
abstract: Vascular smooth muscle cells (VSMCs) are indispensible components in foam cell formation. Salusin-β is a stimulator in the progression of atherosclerosis. Here, we showed that salusin-β increased foam cell formation evidenced by accumulation of lipid droplets and intracellular cholesterol content, and promoted monocyte adhesion in human VSMCs. Salusin-β increased the expressions and activity of acyl coenzyme A:cholesterol acyltransferase-1 (ACAT-1) and vascular cell adhesion molecule-1 (VCAM-1) in VSMCs. Silencing of ACAT-1 abolished the salusin-β-induced lipid accumulation, and silencing of VCAM-1 prevented the salusin-β-induced monocyte adhesion in VSMCs. Salusin-β caused p65-NFκB nuclear translocation and increased p65 occupancy at the ACAT-1 and VCAM-1 promoter. Inhibition of NFκB with Bay 11-7082 prevented the salusin-β-induced ACAT-1 and VCAM-1 upregulation, foam cell formation and monocyte adhesion in VSMCs. Scavenging ROS, inhibiting NADPH oxidase or knockdown of NOX2 abolished the effects of salusin-β on ACAT-1 and VCAM-1 expressions, p65-NFκB nuclear translocation, lipid accumulation and monocyte adhesion in VSMCs. Salusin-β increased miR155 expression, and knockdown of miR155 prevented the effects of salusin-β on ACAT-1 and VCAM-1 expressions, p65-NFκB nuclear translocation, lipid accumulation, monocyte adhesion and ROS production in VSMCs. These results indicate that salusin-β induces foam formation and monocyte adhesion via miR155/NOX2/NFκB-mediated ACAT-1 and VCAM-1 expressions in VSMCs.
authors.affiliation: Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Hai-Jian
authors.initials: HJ
authors.lastname: Sun
authors.affiliation: Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Ming-Xia
authors.initials: MX
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Tong-Yan
authors.initials: TY
authors.lastname: Liu
authors.affiliation: Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Xing-Sheng
authors.initials: XS
authors.lastname: Ren
authors.affiliation: Department of Pathophysiology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Pathophysiology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Yue-Hua
authors.initials: YH
authors.lastname: Li
authors.affiliation: Department of Physiology and Pathophysiology, Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an 710061, China.
authors.forename: Yu-Ming
authors.initials: YM
authors.lastname: Kang
authors.affiliation: Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.|Department of Pathophysiology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Guo-Qing
authors.initials: GQ
authors.lastname: Zhu
mesh_terms: D000101:Acetyl-CoA C-Acetyltransferase / Q000235:genetics; D002448:Cell Adhesion; D002478:Cells, Cultured; D005487:Foam Cells / Q000166:cytology*; D005786:Gene Expression Regulation; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; C524942:MIRN155 microRNA, human; D008562:Membrane Glycoproteins; D035683:MicroRNAs; D016328:NF-kappa B; D017382:Reactive Oxygen Species; C478739:TOR2A protein, human; D019010:Vascular Cell Adhesion Molecule-1; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C506639:ACAT1 protein, human; D000101:Acetyl-CoA C-Acetyltransferase