VISFATIN PROMOTES FOAM CELL FORMATION BY DYSREGULATING CD36, SRA, ABCA1, AND ABCG1 EXPRESSION IN RAW264.7 MACROPHAGES

• Published in: Shock (Augusta, Ga.) Ga.), 2016-04, Vol.45 (4), p.460-468
• Main Authors: Lin, Yu-Ting, Jian, Deng-Yuan, Kwok, Ching-Fai, Ho, Low-Tone, Juan, Chi-Chang
• Format: Article
• Language: English
• Subjects: Animals; Atherosclerosis - metabolism; Atherosclerosis - pathology; ATP Binding Cassette Transporter 1 - biosynthesis; ATP Binding Cassette Transporter, Sub-Family G, Member 1 - biosynthesis; CD36 Antigens - biosynthesis; Cell Line; Cytokines - metabolism; Foam Cells - metabolism; Foam Cells - pathology; Gene Expression Regulation; MAP Kinase Signaling System; Mice; Nicotinamide Phosphoribosyltransferase - metabolism; Receptors, Scavenger - biosynthesis
• ISSN: 1073-2322; 1540-0514
• DOI: 10.1097/SHK.0000000000000529

BACKGROUND:Visfatin is produced in and secreted from adipocytes. Increased circulating visfatin level is observed in obese subjects. Previous studies demonstrated that visfatin was involved in obesity-related cardiovascular diseases. AIMS:This study aims to explore the regulatory effects of adipokine visfatin on foam cell formation, a key step in the development of atherosclerosis. METHODS:Effect of visfatin on protein and mRNA expression of scavenger receptor and ATP binding cassette transporter in RAW264.7 macrophages were measured by western blotting and real-time RT-PCR. To confirm the influence of visfatin-regulated scavenger receptor and ATP binding cassette transporter to foam cell formation, the visfatin-caused changes of ox-LDL uptake, cholesterol efflux, and foam cell formation were determined. RESULTS:Visfatin significantly increased the expression of CD36 and scavenger receptor A (SRA), decreased the expression of ATP-binding cassette transporters A1 (ABCA1) and G1 (ABCG1), and had no effect on the expression of SR-B1. Visfatin increased oxidized-LDL (ox-LDL) uptake and decreased cholesterol efflux, which increased foam cell formation. The PI3K inhibitor LY294002 blocked the effect of visfatin on the protein and mRNA expression levels of CD36, SRA, and ABCG1 and ox-LDL uptake and cholesterol efflux. The ERK inhibitor PD98059 also prevented visfatin-induced ABCA1 instability and subsequently decreased cholesterol efflux. CONCLUSIONS:Visfatin upregulated CD36 and SRA expression and downregulated ABCA1 and ABCG1 expression, subsequently increased ox-LDL uptake and decreased cholesterol efflux, and finally promoted foam cell formation via the PI3K- and ERK-dependent pathways.