EGCG upregulated ABCA1 expression by decreasing miR-33 a generation to reduce lipid accumulation of macrophage-derived foam cells / 中国药理学通报

ABSTRACT

Aim To investigate whether EGCG regu-lates ABCA1 expression by influencing the expression of miR-33 a to promote cholesterol efflux from macro-phages. Methods THP-1 macrophage-derived foam cells were established by co-incubated with oxLDL, and then treated with EGCG, and miR-33a expression was detected with Real-time PCR. THP-1 macrophage-derived foam cells were randomly divided into the fol-lowing groups control group, 50 μmol · L-1 EGCG treatment group, 50 μmol · L-1 EGCG +80 nmol · L-1 miR-33a mimic treated group. Real-time PCR and Werstern blot was used to detect ABCA1 mRNA and protein expression, Oil Red O staining and high per-formance liquid chromatography were used to detect in-tracellular lipid content, and [3H] assay was used to determine cellular cholesterol efflux. Results EGCG could downregulate miRNA33 a expression in a dose-and time-dependent fashion within safe doses. EGCG significantly upregulated ABCA1 mRNA and protein expression, which could be inhibited after miRNA33 mimic transfected into cells, however. EGCG may re-duce lipid accumulation in THP-1 macrophage-derived foam cells, and this effect could also be weakened after miRNA33 mimic transfected. EGCG could reduce the accumulation of intracellular cholesterol,which was re-lated with EGCG promoting intracellular cholesterol ef-flux , and excess miRNA33 a transfected into cells could inhibit intracellular cholesterol efflux. Conclusion EGCG may upregulate ABCA1 expression by reducing miRNA33a generation, resulting in the promotion of cholesterol efflux from macrophages, which may be one of the molecular mechanisms of EGCG anti-atheroscle-rotic effect.