Apelin-13 Inhibits Lipoprotein Lipase Expression Via The APJ/PKCα/miR-361-5p Signaling Pathway In THP-1 Macrophage-derived Foam Cells

Background and Aims:Accumulating evidence suggests that apelin-13 has protective effects on cardiovascular diseases,but the mechanism is unknown.Macrophage-derived lipoprotein lipase(LPL)might be a key factor that promotes atherosclerosis by accelerating lipid accumulation and the secretion of proinflammatory cytokine.Here,miR-361-5p was identified to bind to the 3’UTR of LPL.In this study,we aimed at exploring whether apelin-13 affected the accumulation of lipid and the secretion of pro-inflammatory cytokines by targeting LPL and its underlying mechanism in THP-1 macrophage-derived foam cells.Aim: To investigate the effect of apelin-13 on LPL expression in THP-1 macrophage-derived foam cells,the accumulation of lipid and the secretion of pro-inflammatory cytokines.Methodsand Results: THP-1 macrophage-derived foam cells were administrated with or without apelin-13,followed by investigating lipid accumulation,proinflammatory cytokine secretion and underlying mechanism.HPLC and Elisa method indicated that apelin-13 decreased lipid accumulationand the secretion ofproinflammatory cytokine.Meanwhile,our research demonstrated that apelin-13 activated PKCα,and promoted the expression of miR-361-5p.Moreover,bioinformatics analyses and dual-luciferase reporter assays showed that miR-361-5p directly downregulated the expression of LPL by targeting the 3’UTR of LPL.Taken together,these data suggested that apelin-13 activated PKCα,promoted the expression of miR-361-5p and inhibited LPL expression,thereby decreasing the secretion of pro-inflammatory cytokine and lipid accumulation in THP-1 macrophage-derived foam cells.Conclusions: Apelin-13 inhibits LPL expression via activating the APJ/PKCα/miR-361-5p signaling pathway in THP-1 macrophage-derived foam cells,resulting in inhibition of lipid accumulation and the secretion of pro-inflammatory cytokine.