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 [³H]‐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.

中文翻译：

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MicroRNA-328-5p 通过组蛋白脱乙酰酶 3/ATP 结合盒转运蛋白 A1 通路减轻巨噬细胞脂质积累

据报道，MicroRNA-328 (miR-328) 可预防动脉粥样硬化，但其在泡沫细胞形成中的作用仍不清楚。本研究的目的是研究 miR-328-5p 对巨噬细胞脂质积累的影响及其潜在机制。结果表明，在氧化低密度脂蛋白 (ox-LDL) 处理的巨噬细胞中，miR-328-5p 的表达显着降低。用 miR-328-5p 模拟物治疗人急性单核细胞白血病细胞 (THP-1) 巨噬细胞衍生的泡沫细胞显着增加 [ ^3]H]-胆固醇流出，抑制脂滴积累，降低细胞内总胆固醇（TC）、游离胆固醇（FC）和胆固醇酯（CE）含量。miR-328-5p 的上调也降低了组蛋白去乙酰化酶 3 (HDAC3) 的表达，但增加了 THP-1 巨噬细胞来源的泡沫细胞中 ATP 结合盒转运蛋白 A1 (ABCA1) 的水平。从机制上讲，miR-328-5p 通过直接靶向 3'UTR 抑制 HDAC3 表达，从而促进 ABCA1 表达和随后的胆固醇流出。此外，miR-328-5p 不影响 Dil-ox-LDL 的摄取或清道夫受体-A (SR-A)、血小板反应蛋白受体 (CD36) 和 ABCG1 的表达。总之，这些发现表明 miR-328-5p 通过 HDAC3/ABCA1 途径减轻巨噬细胞脂质积累。