Atherosclerotic lesions are characterized by the accumulation of abundant lipids and chronic inflammation.Previous researches have indicated that macrophage-derived lipoprotein lipase (LPL) promotes atherosclerosis progression by accelerating lipid accumulation and proinflammatory cytokine secretion.Although apelin-13 has been regarded as an atheroprotective factor,it remains unclear whether it can regulate the expression of LPL.The aim of this study was to explore the effects of apelin-13 on the expression of LPL and the underlying mechanism in THP-1 macrophage-derived foam cells.Apelin-13 significantly decreased cellular levels of total cholesterol,free cholesterol,and cholesterol ester at the concentrations of 10 and 100 nM.ELISA analysis confirmed that treatment with apelin-13 reduced pro-inflammatory cytokine secretion,such as interleukin-6 (IL-6),interleukin-1β (IL-1β) and tumor necrosis factor-alpha (TNF-α).It was also found that apelin-13 inhibited the expression of LPL as revealed by western blot and real-time PCR analyses.Bioinformatics analyses and dual-luciferase reporter assay indicated that miR-361-5p directly downregulated the expression of LPL by targeting the 3'UTR of LPL.In addition,apelin-13 + miR-361-5p mimic significantly downregulated the expression of LPL in cells.Finally,we demonstrated that apelin-13 downregulated the expression of LPL through activating the activity of PKCα.Taken together,our results showed that apelin-13 downregulated the expression of LPL via activating the APJ/PKCαdmiR-361-5p signaling pathway in THP-1 macrophage-derived foam cells,leading to inhibition of lipid accumulation and proinflammatory cytokine secretion.Therefore,our studies provide important new insight into the inhibition of lipid accumulation and pro-inflammatory cytokine secretion by apelin-13,and highlight apelin-13 as a promising therapeutic target in atherosclerosis.
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