Macrophage-derived foam cells are a major component of atherosclerotic plaques and have an important role in the progression of atherosclerotic plaques, thus posing a great threat to human health. Photodynamic therapy (PDT) has emerged as a therapeutic strategy for atherosclerosis. Here, we investigated the effect of PDT mediated by upconversion fluorescent nanoparticles encapsulating chlorin e6 (UCNPs-Ce6) on the cholesterol efflux of THP-1 macrophage-derived foam cells and explored the possible mechanism of this effect. First, we found that PDT notably enhanced the cholesterol efflux and the induction of autophagy in both THP-1 and peritoneal macrophage-derived foam cells. The autophagy inhibitor 3-methyladenine and an ATG5 siRNA significantly attenuated PDT-induced autophagy, which subsequently suppressed the ABCA1-mediated cholesterol efflux. Furthermore, the reactive oxygen species (ROS) produced by PDT were responsible for the induction of autophagy, which could be blocked by the ROS inhibitor N-acetyl cysteine (NAC). NAC also reversed the PDT-induced suppression of p-mTOR and p-Akt. Therefore, our findings demonstrate that PDT promotes cholesterol efflux by inducing autophagy, and the autophagy was mediated in part through the ROS/PI3K/Akt/mTOR signaling pathway in THP-1 and peritoneal macrophage-derived foam cells.

译文

巨噬细胞衍生的泡沫细胞是动脉粥样硬化斑块的主要成分,在动脉粥样硬化斑块的进展中具有重要作用,因此对人类健康构成了巨大威胁。光动力疗法 (PDT) 已成为动脉粥样硬化的治疗策略。在这里,我们研究了封装了氯蛋白e6 (UCNPs-Ce6) 的上转换荧光纳米颗粒介导的PDT对THP-1巨噬细胞衍生泡沫细胞胆固醇流出的影响,并探索了这种作用的可能机制。首先,我们发现PDT显着增强了THP-1和腹膜巨噬细胞衍生的泡沫细胞中的胆固醇流出和自噬的诱导。自噬抑制剂3-甲基腺嘌呤和ATG5 siRNA显著减弱了PDT诱导的自噬,随后抑制了ABCA1-mediated胆固醇的流出。此外,PDT产生的活性氧 (ROS) 负责自噬的诱导,这可能被ROS抑制剂N-乙酰半胱氨酸 (NAC) 阻断。NAC还逆转了PDT诱导的p-mTOR和p-Akt的抑制。因此,我们的发现表明,PDT通过诱导自噬促进胆固醇流出,自噬部分通过ROS/PI3K/Akt/mTOR信号通路介导THP-1和腹膜巨噬细胞衍生的泡沫细胞。

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