scholarly journals Sonodynamic Therapy Promotes Efferocytosis via CD47 Down-Regulation in Advanced Atherosclerotic Plaque

2022 ◽  
Author(s):  
Yang Cao ◽  
Jianting Yao ◽  
Weiwei Gao ◽  
Zhengyu Cao ◽  
Kamal Diabakte ◽  
...  
Keyword(s):  
Atherosclerotic Plaque ◽  
Down Regulation ◽  
Sonodynamic Therapy

scholarly journals Elevated cellular PpIX potentiates sonodynamic therapy in a mouse glioma stem cell-bearing glioma model by downregulating the Akt/NFkB/MDR1 pathway

2020 ◽  
Author(s):  
Yoshifumi Mizobuchi ◽  
Kenji Shono ◽  
Izumi Yamaguchi ◽  
Kohei Nakajima ◽  
Yuri Fujiwara ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Surgical Intervention ◽  
Aminolevulinic Acid ◽  
Protoporphyrin Ix ◽  
Multidrug Resistant ◽  
Down Regulation ◽  
Sonodynamic Therapy ◽  
Glioma Model ◽  
A Site ◽  
Mouse Glioma

Abstract Glioblastoma (GBM) has high mortality rates because of extremely therapeutic resistance. During surgical resection for GBM, 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence is conventionally applied to distinguish GBM. However, surgical intervention is insufficient for high invasive GBM. Sonodynamic therapy (SDT) is an emerging and promising approach combined with low-intensity ultrasonication (US) and PpIX as a sonosensitizer for cancer, whereas its efficacy is limited. Based on our previous study that down-regulation of multidrug resistant protein (MDR1) in GBM augmented anti-tumor effects of chemotherapy, we hypothesized that elevation of cellular PpIX levels by down-regulation of MDR1 enhances anti-tumor effects by SDT. In high invasive progeny cells from mouse glioma stem cells (GSCs) and a GSC-bearing mouse glioma model, we assessed the anti-tumor effects of SDT with a COX-2 inhibitor, celecoxib. Down-regulation of MDR1 by celecoxib increased cellular PpIX levels, as well as valspodar, a MDR1 inhibitor and augmented anti-tumor effects of SDT. MDR1 down-regulation via Akt/NF-kB pathway by celecoxib was confirmed, using a NF-kB inhibitor, CAPÉ. Thus, elevation of cellar PpIX by down-regulation of MDR1 via Akt/NF-kB pathway may be crucial to potentiate the efficacy of SDT in a site-directed manner and provide a promising new therapeutic strategy for GBM.

Rapid stabilisation of atherosclerotic plaque with 5-aminolevulinic acid-mediated sonodynamic therapy

2015 ◽  
Vol 114 (10) ◽  
pp. 793-803 ◽  
Author(s):  
Liping Wang ◽  
Tengyu Wang ◽  
Chenghai Peng ◽  
Wei Wang ◽  
Zhen Tian ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Atherosclerotic Plaque ◽  
Aminolevulinic Acid ◽  
Apoptotic Cell ◽  
Tube Placement ◽  
Sonodynamic Therapy ◽  
Percentage Content ◽  
Plaque Disruption ◽  
Plaque Stabilisation

Summary5-Aminolevulinic acid-mediated sonodynamic therapy (ALA-SDT) effectively induces the apoptosis of atherogenic macrophages, but whether it can stabilise atherosclerotic plaque in vivo is unclear. Here, we used an animal model to evaluate the effects of ALA-SDT on plaque stabilisation. Sixty rabbits were induced atherosclerotic plaques in the femoral artery with a combination of silastic tube placement with atherogenic diet, and randomly assigned into control (n = 12) and SDT (n = 48) groups. In the SDT group, after intravenous injected with ALA (60 mg/kg) animals underwent the treatment of ultrasound with intensities of 0.75, 1.00, 1.50 and 2.00 W/cm2 (n = 12 for each intensity). Seven days after the treatment, the plaque disruption assay was performed to test plaque stability. We found that ALA-SDT with ultrasound intensity of 1.5 W/cm2 showed the strongest efficacy to stabilise plaques. Under this condition, the frequency of plaque disruption decreased by 88 % (p < 0.01), positive area of macrophages reduced by 94 % (p < 0.001) and percentage content of lipids dropped by 60 % (p < 0.001), while percentage content of collagens increased by 127 % (p < 0.001). We also found that the plaque stabilisation by ALA-SDT was associated with increased macrophage apoptosis and apoptotic cell clearance. Moreover, ALA-SDT decreased the contents and activities of matrix metalloproteinase-2,9 and increased the levels of tissue inhibitors of matrix metalloproteinase-1,2 in plaques. Our studies demonstrate that ALA-SDT promotes plaque stabilisation by inducing macrophage elimination and inhibiting matrix degradation. This method might be a promising regimen for atherosclerosis therapy.

scholarly journals Non-Lethal Sonodynamic Therapy Inhibits Atherosclerotic Plaque Progression in ApoE-/- Mice and Attenuates ox-LDL-mediated Macrophage Impairment by Inducing Heme Oxygenase-1

2017 ◽  
Vol 41 (6) ◽  
pp. 2432-2446 ◽  
Author(s):  
Yu Wang ◽  
Wei Wang ◽  
Haobo Xu ◽  
Yan Sun ◽  
Jing Sun ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Western Blotting ◽  
Heme Oxygenase ◽  
Atherosclerotic Plaque ◽  
Heme Oxygenase 1 ◽  
Atherosclerotic Plaques ◽  
Protective Effects ◽  
Plaque Progression ◽  
Sonodynamic Therapy ◽  
Low Intensity

Background: Previous studies from our group showed that low-intensity sonodynamic therapy (SDT) has protective effects on atherosclerosis (AS). However, because the intensity of ultrasound passing through tissue is attenuated, the consequences of very low-intensity SDT, referred to as non-lethal SDT (NL-SDT), on atherosclerotic plaques are unclear. The aim of this study was to determine whether NL-SDT affects atherosclerotic plaques and to elucidate the possible underlying mechanisms. Methods: An AS model was established using ApoE-/- mice fed a western diet. En face Oil Red O staining was used to measure atherosclerotic plaque size. Hematoxylin and eosin staining and immunohistochemical staining were used to observe plaque morphology and assess the location of macrophages and heme oxygenase 1 (HO-1). HO-1 mRNA and protein levels in AS plaques were evaluated by real-time PCR and western blotting. Human THP-1 cells and mouse peritoneal macrophages were used in this study. Western blotting was used to investigate the expression of cellular proteins after NL-SDT. Macrophage apoptosis was evaluated by TUNEL assays and flow cytometry with Annexin V/PI double staining. Intracellular reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were measured with 2′-7′-dichlorofluorescein diacetate (DCFH-DA) and 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethyl benzimidazolyl carbocyanine iodide (JC-1) staining, respectively. Results: NL-SDT significantly inhibited AS progression and reduced the necrotic core area. NL-SDT induced HO-1 expression in lesional macrophages and in cultured macrophages. NL-SDT activated the protein kinase B (AKT) and extracellular signal-related protein kinase (ERK) pathways and the transcription factor NF-E2-related factor 2 (Nrf2).NL-SDT significantly reduced oxidized LDL (ox-LDL)-induced macrophage MMP collapse, ROS production and cell apoptosis. Zinc protoporphyrin (ZnPP), a HO-1-specific inhibitor, reversed the protective effects of NL-SDT. Conclusion: NL-SDT inhibits atherosclerotic plaque progression and increases plaque stability. In vitro, NL-SDT has a protective effect on ox-LDL-induced macrophage impairment via HO-1.

Rapid inhibition of atherosclerotic plaque progression by sonodynamic therapy

2018 ◽  
Vol 115 (1) ◽  
pp. 190-203 ◽  
Author(s):  
Xin Sun ◽  
Shuyuan Guo ◽  
Jianting Yao ◽  
Huan Wang ◽  
Chenghai Peng ◽  
...  
Keyword(s):  
Atherosclerotic Plaque ◽  
Standard Of Care ◽  
Atherosclerotic Plaques ◽  
Plaque Progression ◽  
Peripheral Artery ◽  
Sonodynamic Therapy ◽  
Non Invasive ◽  
Atherosclerotic Burden ◽  
Artery Disease ◽  
Apoe Deficient Mouse

Abstract Aims Currently, efficient regimens to reverse atherosclerotic plaques are not available in the clinic. Herein, we present sonodynamic therapy (SDT) as a novel methodology to rapidly inhibit progression of atherosclerotic plaques. Methods and results In atherosclerotic rabbit and apoE-deficient mouse models, SDT efficiently decreased the atherosclerotic burden within 1 week, revealing a decrease in the size of the atherosclerotic plaque and enlarged lumen. The shrunken atherosclerotic plaques displayed compositional alterations, with a reduction in lesional macrophages and lipids. The rapid efficacy of SDT may be due to its induction of macrophage apoptosis, enhancement of efferocytosis, and amelioration of inflammation in the atherosclerotic plaque. Compared with atorvastatin, the standard of care for atherosclerosis, SDT showed more significant plaque shrinkage and lumen enlargement during 1 week treatment. Furthermore, SDT displayed good safety without obvious side effects. In a pilot clinical trial recruiting the patients suffering atherosclerotic peripheral artery disease, combination therapy of SDT with atorvastatin efficiently reduced progression of atherosclerotic plaque within 4 weeks, and its efficacy was able to last for at least 40 weeks. Conclusion SDT is a non-invasive and efficacious regimen to inhibit atherosclerotic plaque progression.

scholarly journals Elevated cellular PpIX potentiates sonodynamic therapy in a mouse glioma stem cell-bearing glioma model by downregulating the Akt/NF-κB/MDR1 pathway

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kenji Shono ◽  
Yoshifumi Mizobuchi ◽  
Izumi Yamaguchi ◽  
Kohei Nakajima ◽  
Yuri Fujiwara ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Surgical Intervention ◽  
Aminolevulinic Acid ◽  
Protoporphyrin Ix ◽  
Multidrug Resistant ◽  
Down Regulation ◽  
Sonodynamic Therapy ◽  
Glioma Model ◽  
A Site ◽  
Mouse Glioma

AbstractGlioblastoma (GBM) has high mortality rates because of extreme therapeutic resistance. During surgical resection for GBM, 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence is conventionally applied to distinguish GBM. However, surgical intervention is insufficient for high invasive GBM. Sonodynamic therapy (SDT) combined with low-intensity ultrasonication (US) and PpIX, as a sonosensitizer, is an emerging and promising approach, although its efficacy is limited. Based on our previous study that down-regulation of multidrug resistant protein (MDR1) in GBM augmented the anti-tumor effects of chemotherapy, we hypothesized that elevation of cellular PpIX levels by down-regulation of MDR1 enhances anti-tumor effects by SDT. In high invasive progeny cells from mouse glioma stem cells (GSCs) and a GSC-bearing mouse glioma model, we assessed the anti-tumor effects of SDT with a COX-2 inhibitor, celecoxib. Down-regulation of MDR1 by celecoxib increased cellular PpIX levels, as well as valspodar, an MDR1 inhibitor, and augmented anti-tumor effects of SDT. MDR1 down-regulation via the Akt/NF-κB pathway by celecoxib was confirmed, using an NF-κB inhibitor, CAPÉ. Thus, elevation of cellar PpIX by down-regulation of MDR1 via the Akt/NF-κB pathway may be crucial to potentiate the efficacy of SDT in a site-directed manner and provide a promising new therapeutic strategy for GBM.

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