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

Vascular smooth muscle cells (VSMCs) are indispensible components in foam cell formation. Salusin-beta is a stimulator in the progression of atherosclerosis. Here, we showed that salusin-beta increased foam cell formation evidenced by accumulation of lipid droplets and intracellular cholesterol content, and promoted monocyte adhesion in human VSMCs. Salusin-beta 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-beta-induced lipid accumulation, and silencing of VCAM-1 prevented the salusin-beta-induced monocyte adhesion in VSMCs. Salusin-beta caused p65-NF kappa B nuclear translocation and increased p65 occupancy at the ACAT-1 and VCAM-1 promoter. Inhibition of NF kappa B with Bay 11-7082 prevented the salusin-beta-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-beta on ACAT-1 and VCAM-1 expressions, p65-NF kappa B nuclear translocation, lipid accumulation and monocyte adhesion in VSMCs. Salusin-beta increased miR155 expression, and knockdown of miR155 prevented the effects of salusin-beta on ACAT-1 and VCAM-1 expressions, p65-NF kappa B nuclear translocation, lipid accumulation, monocyte adhesion and ROS production in VSMCs. These results indicate that salusin-beta induces foam formation and monocyte adhesion via miR155/NOX2/NF kappa B-mediated ACAT-1 and VCAM-1 expressions in VSMCs.