Salusin-? induces foam cell formation and monocyte adhesion in human vascular smooth muscle cells via miR155/NOX2/NF?B pathway.

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

SUBMITTER: Sun HJ 

PROVIDER: S-EPMC4804242 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature