Abstract |
Emerging evidence indicates that macrophage functional polarization is critically involved in the development of atherosclerosis (AS). Here, we examined the role of 5-aminolaevulinic acid (ALA)-mediated non-lethal sonodynamic therapy (NL-SDT) in macrophage-subset polarization and atherosclerotic lesion stability and explored the potential underlying mechanisms. Using Western diet-fed apolipoprotein E ( apoE)-/- and green fluorescent protein (GFP)-positive bone marrow (BM) chimeric mouse models, we demonstrated that NL-SDT promoted phenotypic switching of both BM-derived and resident macrophages from M1 to M2 and significantly inhibited AS progression. Further mechanistic studies indicated that NL-SDT enhanced macrophage differentiation toward the M2 phenotype by activating the reactive oxygen species (ROS)-5' AMP-activated protein kinase (AMPK)- mammalian target of rapamycin complex 1 (mTORC1)-autophagy signaling pathway in murine BM-derived M1 macrophages (BMDM1s). Moreover, NL-SDT drastically reduced lipid droplets, mainly by promoting apoAI-mediated cholesterol efflux in vitro. Specifically, administration of pharmacological inhibitors to the animal model showed a reciprocal effect on NL-SDT-induced macrophage polarization. These findings indicate that NL-SDT engages a virtuous cycle that enhances M1-to-M2 polarization, cholesterol efflux, and anti-inflammatory reactions in advanced plaque in vivo and in BMDM1s in vitro by activating the ROS-AMPK-mTORC1-autophagy pathway. This discovery might help elucidate the mechanism underlying NL-SDT as a potential treatment to prevent atherothrombotic events.
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Authors | Yang Yang, Jiayu Wang, Shuyuan Guo, Shirin Pourteymour, Qiulian Xu, Jie Gong, Zhen Huang, Zhaoqian Shen, Kamal Diabakte, Zhengyu Cao, Guodong Wu, Sukhareva Natalia, Zhen Tian, Hong Jin, Ye Tian |
Journal | Redox biology
(Redox Biol)
Vol. 32
Pg. 101501
(05 2020)
ISSN: 2213-2317 [Electronic] Netherlands |
PMID | 32179242
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved. |
Chemical References |
- Reactive Oxygen Species
- AMP-Activated Protein Kinases
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Topics |
- AMP-Activated Protein Kinases
- Animals
- Atherosclerosis
- Autophagy
- Mice
- Plaque, Atherosclerotic
- Reactive Oxygen Species
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