Macrophage-derived foam cells formation is the initial stage of atherosclerosis, and lipid-laden macrophage accumulation is also considered as the symbol of unstable plaque. Autophagy is a subcellular process responsible for the degradation of damaged organelles and aggregated proteins in cells (Grootaert in Oxid Med Cell Longev: 7687083, 2018). Macrophage autophagy plays an important role in atherosclerosis under various stress conditions, and microRNAs are involved in this complicated process. The present study was programmed to explore the effects of microRNA-761 on macrophage-derived foam cell formation, focusing on the role of autophagy in this pathological process. The differentiated human THP-1 macrophages were used in the study. THP-1-derived macrophages were treated with miR-761 mimics or inhibitors and cultured with oxidized low-density lipoprotein to mimic the lipid-rich environment in blood vessel. The expression of miR-761 and mRNA levels of IL-1β and IL-18 were analyzed by quantitative real-time PCR. The effect of miR-761 on autophagy was evaluated by the protein levels of Beclin1, p62/SQSTM1, microtubule-associated protein light chain 3, mammalian target of rapamycin (mTOR), and unc-51-like autophagy activating kinase 1 (ULK1), determined by immunoblot and autophagic flux detected by fluorescent staining. The secretion of IL-1β and IL-18 was tested by enzyme-linked immunosorbent reaction kit. Lipid accumulation in foam cells was detected by oil red "O" staining. We demonstrated that miR-761 was able to repress foam cell formation and reduce the production of atherogenic inflammatory cytokines IL-1β and IL-18 in an autophagy-dependent manner in atherosclerosis, possibly via mTOR-ULK1 signaling pathway. In summary, we described an athero-protective function of miR-761 in macrophages incubated with excess ox-LDL and identified an important novel modulator of mTOR signaling and autophagy in macrophage-derived foam cells. This finding may provide a potential target for the prevention and early treatment in high-risk group of atherosclerosis.

巨噬细胞源性泡沫细胞的形成是动脉粥样硬化的初始阶段，而载脂类巨噬细胞的积累也被认为是不稳定斑块的象征。自噬是一个亚细胞过程，负责细胞中受损细胞器和聚集蛋白的降解（Grootaert in Oxid Med Cell Longev：7687083，2018）。巨噬细胞自噬在各种压力条件下的动脉粥样硬化中起着重要作用，而microRNA参与了这个复杂的过程。本研究程序旨在探讨microRNA-761对巨噬细胞衍生的泡沫细胞形成的影响，重点是自噬在此病理过程中的作用。在研究中使用分化的人类THP-1巨噬细胞。用miR-761模拟物或抑制剂处理THP-1衍生的巨噬细胞，并用氧化的低密度脂蛋白进行培养，以模拟血管中富含脂质的环境。通过实时定量PCR分析miR-761的表达以及IL-1β和IL-18的mRNA水平。通过Beclin1，p62 / SQSTM1，微管相关蛋白轻链3，哺乳动物雷帕霉素靶标（mTOR）和unc-51-like自噬激活激酶1（ULK1）的蛋白水平评估miR-761对自噬的影响。通过免疫印迹测定，通过荧光染色检测自噬通量。用酶联免疫吸附试剂盒检测IL-1β和IL-18的分泌。通过油红色“ O”染色检测泡沫细胞中的脂质蓄积。我们证明，miR-761可以通过mTOR-ULK1信号通路以自噬依赖性方式抑制动脉粥样硬化中泡沫细胞的形成并减少动脉粥样硬化炎性细胞因子IL-1β和IL-18的产生。总之，我们描述了miR-761在与过量ox-LDL孵育的巨噬细胞中的动脉粥样硬化保护功能，并鉴定了巨噬细胞衍生泡沫细胞中mTOR信号转导和自噬的重要新型调节剂。这一发现可能为动脉粥样硬化高危人群的预防和早期治疗提供潜在的靶标。我们描述了在与过量ox-LDL孵育的巨噬细胞中miR-761的动脉粥样硬化保护功能，并确定了巨噬细胞衍生泡沫细胞中mTOR信号转导和自噬的重要新型调节剂。这一发现可能为动脉粥样硬化高危人群的预防和早期治疗提供潜在的靶标。我们描述了miR-761在与过量ox-LDL孵育的巨噬细胞中的动脉粥样硬化保护功能，并确定了巨噬细胞衍生泡沫细胞中mTOR信号转导和自噬的重要新型调节剂。这一发现可能为动脉粥样硬化高危人群的预防和早期治疗提供潜在的靶标。