期刊
CELL DEATH & DISEASE
卷 8, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/cddis.2017.242
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资金
- National Natural Science Foundation of China [81571833, 81271734, 81000688, 81300200]
- Heilongjiang Provincial Science Foundation [H2015006]
- Foundation of Science and Technology Innovation Talent of Harbin Science and Technology Bureau [2015RAQXJ100]
- Wu Liande Youth Science Foundation of Harbin Medical University [WLD-QN1104]
- Postdoctoral Science-Research Developmental Foundation of Heilongjiang Province [LBHQ12049]
- Harbin Medical University Cancer Hospital
- Postgraduate Innovation Foundation of Harbin Medical University [YJSCX2015-33HYD, YJSCX2016-37HYD]
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.
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