Key result
Apelin-13 downregulates LPL and reduces macrophage lipid accumulation via the APJ/PKCα/miR-361-5p pathway.
Why the study?
It remains unclear whether apelin-13 can regulate the expression of macrophage-derived lipoprotein lipase, which promotes atherosclerosis progression.
Does not support clinical use of apelin-13; leaves open its therapeutic role in atherosclerosis pending in vivo validation.
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 pro-inflammatory 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/PKCα/miR-361-5p signaling pathway in THP-1 macrophage-derived foam cells, leading to inhibition of lipid accumulation and pro-inflammatory 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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Zhang et al. (2017) studied Atherosclerosis (in vitro model). Apelin-13 was evaluated on Lipoprotein lipase (LPL) expression, lipid accumulation, and pro-inflammatory cytokine secretion. Apelin-13 downregulated LPL expression via the APJ/PKCα/miR-361-5p signaling pathway in THP-1 macrophage-derived foam cells, inhibiting lipid accumulation and pro-inflammatory cytokine secretion.
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