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声动力疗法可降低出血性斑块的铁潴留。

Sonodynamic therapy reduces iron retention of hemorrhagic plaque.

作者信息

Li Bicheng, Gong Jie, Sheng Siqi, Lu Minqiao, Guo Shuyuan, Yao Jianting, Zhang Haiyu, Zhao Xuezhu, Cao Zhengyu, Sun Xin, Wang Huan, Cao Yang, Jiang Yongxing, Tian Zhen, Liu Bin, Zhao Hua, Zhang Zhiguo, Jin Hong, Tian Ye

机构信息

Department of Cardiology, The First Affiliated Hospital, Cardiovascular Institute Harbin Medical University Harbin People's Republic of China.

Department of Pathophysiology and Key Laboratory of Cardiovascular Pathophysiology Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education Harbin People's Republic of China.

出版信息

Bioeng Transl Med. 2020 Oct 31;6(1):e10193. doi: 10.1002/btm2.10193. eCollection 2021 Jan.

DOI:10.1002/btm2.10193
PMID:33532592
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7823128/
Abstract

Intraplaque hemorrhage (IPH) plays a major role in the aggressive progression of vulnerable plaque, leading to acute cardiovascular events. We previously demonstrated that sonodynamic therapy (SDT) inhibits atherosclerotic plaque progression. In this study, we investigated whether SDT could also be applied to treat more advanced hemorrhagic plaque and addressed the underlying mechanism. SDT decreased atherosclerotic burden, positively altered atherosclerotic lesion composition, and alleviated iron retention in rabbit hemorrhagic plaques. Furthermore, SDT reduced iron retention by stimulating expression in () mouse plaques with high susceptibility to IPH. Subsequently, SDT inhibited iron-overload-induced foam-cell formation and pro-inflammatory cytokines secretion in vitro. Moreover, SDT reduced levels of the labile iron pool and expression via the reactive oxygen species (ROS)-nuclear factor erythroid 2-related factor 2 (Nrf2)-FPN1 pathway. SDT exerted therapeutic effects on hemorrhagic plaques and reduced iron retention via the ROS-Nrf2-FPN1 pathway in macrophages, thereby suggesting that it is a potential translational strategy for patients with advanced atherosclerosis in clinical practice.

摘要

斑块内出血（IPH）在易损斑块的进展中起主要作用，导致急性心血管事件。我们之前证明了声动力疗法（SDT）可抑制动脉粥样硬化斑块进展。在本研究中，我们调查了SDT是否也可用于治疗更晚期的出血性斑块，并探讨了其潜在机制。SDT减轻了兔出血性斑块的动脉粥样硬化负担，积极改变了动脉粥样硬化病变组成，并减轻了铁潴留。此外，SDT通过刺激对IPH高度敏感的（）小鼠斑块中的表达来减少铁潴留。随后，SDT在体外抑制了铁过载诱导的泡沫细胞形成和促炎细胞因子分泌。此外，SDT通过活性氧（ROS）-核因子红细胞2相关因子2（Nrf2）-FPN1途径降低了不稳定铁池水平和表达。SDT对出血性斑块具有治疗作用，并通过ROS-Nrf2-FPN1途径减少巨噬细胞中的铁潴留，从而表明它是临床实践中晚期动脉粥样硬化患者的一种潜在转化策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/958f/7823128/9c1c1196d839/BTM2-6-e10193-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/958f/7823128/c20d2c07b953/BTM2-6-e10193-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/958f/7823128/51d89c80748f/BTM2-6-e10193-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/958f/7823128/983a7ba46e24/BTM2-6-e10193-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/958f/7823128/a49d50dcdcb7/BTM2-6-e10193-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/958f/7823128/e9a1dd47acf4/BTM2-6-e10193-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/958f/7823128/98ab62295677/BTM2-6-e10193-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/958f/7823128/9c1c1196d839/BTM2-6-e10193-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/958f/7823128/c20d2c07b953/BTM2-6-e10193-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/958f/7823128/51d89c80748f/BTM2-6-e10193-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/958f/7823128/983a7ba46e24/BTM2-6-e10193-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/958f/7823128/a49d50dcdcb7/BTM2-6-e10193-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/958f/7823128/e9a1dd47acf4/BTM2-6-e10193-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/958f/7823128/98ab62295677/BTM2-6-e10193-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/958f/7823128/9c1c1196d839/BTM2-6-e10193-g007.jpg

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本文引用的文献

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Rapid reduction in plaque inflammation by sonodynamic therapy inpatients with symptomatic femoropopliteal peripheral artery disease:A randomized controlled trial.超声动力疗法治疗症状性股腘周围动脉疾病患者斑块炎症的快速消退：一项随机对照试验。
Int J Cardiol. 2021 Feb 15;325:132-139. doi: 10.1016/j.ijcard.2020.09.035. Epub 2020 Sep 20.
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The Application of DVDMS as a Sensitizing Agent for Sono-/Photo-Therapy.DVDMS作为声/光治疗增敏剂的应用
Front Pharmacol. 2020 Feb 7;11:19. doi: 10.3389/fphar.2020.00019. eCollection 2020.
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Sonodynamic Therapy Suppresses Neovascularization in Atherosclerotic Plaques via Macrophage Apoptosis-Induced Endothelial Cell Apoptosis.
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Nanomedicine for Diagnosis and Treatment of Atherosclerosis.纳米医学用于动脉粥样硬化的诊断和治疗。
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Recent Advances for Dynamic-Based Therapy of Atherosclerosis.基于动力学的动脉粥样硬化治疗新进展。
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声动力疗法通过巨噬细胞凋亡诱导的内皮细胞凋亡抑制动脉粥样硬化斑块中的新生血管形成。
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Atherosclerosis is aggravated by iron overload and ameliorated by dietary and pharmacological iron restriction.铁过载会加重动脉粥样硬化，而饮食和药物性铁限制则可改善动脉粥样硬化。
Eur Heart J. 2020 Jul 21;41(28):2681-2695. doi: 10.1093/eurheartj/ehz112.
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Cardiovasc Res. 2019 Jan 1;115(1):190-203. doi: 10.1093/cvr/cvy139.