MicroRNA‐328‐5p Alleviates Macrophage Lipid Accumulation through the Histone Deacetylase 3/ATP‐binding cassette transporter A1 pathway

Abstract MicroRNA‐328 (miR‐328) was reported to protect against atherosclerosis, but its role in foam cell formation remains unknown. The aim of this study was to investigate the effect of miR‐328‐5p on macrophage lipid accumulation and the underlying mechanisms. The results showed that miR‐328‐5p expression was robustly decreased in oxidized low‐density lipoprotein (ox‐LDL)‐treated macrophages. Treatment of human acute monocytic leukemia cel (THP‐1) macrophage‐derived foam cells with a miR‐328‐5p mimic markedly increased [ 3 H]‐cholesterol efflux, inhibited lipid droplet accumulation, and decreased intracellular total cholesterol (TC), free cholesterol (FC) and cholesteryl ester (CE) contents. Upregulation of miR‐328‐5p also reduced the expression of histone deacetylase 3 (HDAC3) but increased the levels of ATP‐binding cassette transporter A1 (ABCA1) in THP‐1 macrophage‐derived foam cells. Mechanistically, miR‐328‐5p inhibited HDAC3 expression by directly targeting its 3′UTR, thereby promoting ABCA1 expression and the subsequent cholesterol efflux. Furthermore, miR‐328‐5p mimic treatment did not affect the uptake of Dil‐ox‐LDL or the expression of scavenger receptor‐A (SR‐A), thrombospondin receptor (CD36) and ABCG1. Taken together, these findings suggest that miR‐328‐5p alleviates macrophage lipid accumulation through the HDAC3/ABCA1 pathway.