Salusin-β induces foam cell formation and monocyte adhesion in human vascular smooth muscle cells via miR155/NOX2/NFκB pathway

• Published in: Scientific reports 2016-03, Vol.6 (1), p.23596-23596, Article 23596
• Main Authors: Sun, Hai-Jian, Zhao, Ming-Xia, Liu, Tong-Yan, Ren, Xing-Sheng, Chen, Qi, Li, Yue-Hua, Kang, Yu-Ming, Zhu, Guo-Qing
• Format: Article
• Language: English
• Subjects: 38; 38/1; 38/15; 38/77; 38/89; 38/90; 42; 42/89; 631/443/592/75/593/2100; 631/80/86/2366; 82; Acetyl-CoA C-Acetyltransferase - genetics; Cell Adhesion; Cells, Cultured; Foam Cells - cytology; Gene Expression Regulation; Humanities and Social Sciences; Humans; Intercellular Signaling Peptides and Proteins - metabolism; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; MicroRNAs - genetics; Monocytes - cytology; Monocytes - metabolism; multidisciplinary; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - metabolism; NADPH Oxidase 2; NADPH Oxidases - genetics; NADPH Oxidases - metabolism; NF-kappa B - genetics; NF-kappa B - metabolism; Reactive Oxygen Species - metabolism; Science; Signal Transduction; Vascular Cell Adhesion Molecule-1 - genetics
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep23596

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.