...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Redox Biology >Non-lethal sonodynamic therapy facilitates the M1-to-M2 transition in advanced atherosclerotic plaques via activating the ROS–AMPK–mTORC1–autophagy pathway
【24h】

Non-lethal sonodynamic therapy facilitates the M1-to-M2 transition in advanced atherosclerotic plaques via activating the ROS–AMPK–mTORC1–autophagy pathway

机译：非致命的超声动力学治疗通过激活ROS-AMPK-MTORC1-自噬途径促进高级动脉粥样硬化斑块中的M1-〜M2过渡

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

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 )sup ?/? /sup 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.
机译：新兴的证据表明巨噬细胞功能极化批判性地参与动脉粥样硬化（AS）的发展。在这里，我们研究了5-氨基乙酰乙酸（ALA）介导的非致死声学治疗（NL-SDT）在巨噬细胞偏振和动脉粥样硬化病变稳定性中的作用，并探讨了潜在的基础机制。使用西方膳食喂养载脂蛋白E（apoe）？/？ 和绿色荧光蛋白（GFP） - 阳性骨髓（Bm）嵌合小鼠模型，我们证明了NL-SDT促进了BM衍生和常规巨噬细胞的表型切换从M1至M2并显着被抑制为进展。进一步的机械研究表明，通过激活反应性氧物质（ROS）-5'amp-活化的蛋白激酶（AMPK） - 雷帕霉素络合物1（MTORC1） - 急性信号传导途径，NL-SDT增强了对M2表型的巨噬细胞分化鼠BM衍生的M1巨噬细胞（BMDM1S）。此外，NL-SDT大大降低了脂液滴，主要是通过在体外促进Apoai介导的胆固醇流出。具体地，对动物模型的药理抑制剂施用对NL-SDT引起的巨噬细胞极化的互易效应。这些发现表明，NL-SDT通过激活ROS-AMPK-MTORC1自噬途径，将NL-SDT与体内和BMDM1S中的高级斑块中的M1-TO-M2偏振，胆固醇流出和抗炎反应中的抗炎症反应增强。这一发现可能有助于阐明NL-SDT的潜在机制作为预防动脉癌事件的潜在治疗方法。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号