scholarly journals Low-intensity pulsed ultrasound therapy suppresses coronary adventitial inflammatory changes and hyperconstricting responses after coronary stent implantation in pigs in vivo

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257175
Author(s):  
Tasuku Watanabe ◽  
Yasuharu Matsumoto ◽  
Kensuke Nishimiya ◽  
Tomohiko Shindo ◽  
Hirokazu Amamizu ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Stent Implantation ◽  
Sham Group ◽  
Normal Male ◽  
Pulsed Ultrasound ◽  
Low Intensity Pulsed Ultrasound ◽  
Low Intensity ◽  
Coronary Stent Implantation ◽  
Inflammatory Changes

Backgrounds We demonstrated that coronary adventitial inflammation plays important roles in the pathogenesis of drug-eluting stent (DES)-induced coronary hyperconstricting responses in pigs in vivo. However, no therapy is yet available to treat coronary adventitial inflammation. We thus developed the low-intensity pulsed ultrasound (LIPUS) therapy that ameliorates myocardial ischemia by enhancing angiogenesis. Aims We aimed to examine whether our LIPUS therapy suppresses DES-induced coronary hyperconstricting responses in pigs in vivo, and if so, what mechanisms are involved. Methods Sixteen normal male pigs were randomly assigned to the LIPUS or the sham therapy groups after DES implantation into the left anterior descending (LAD) coronary artery. In the LIPUS group, LIPUS (32 cycles, 193 mW/cm2) was applied to the heart at 3 different levels (segments proximal and distal to the stent edges and middle of the stent) for 20 min at each level for every other day for 2 weeks. The sham therapy group was treated in the same manner but without LIPUS. At 4 weeks after stent implantation, we performed coronary angiography, followed by immunohistological analysis. Results Coronary vasoconstricting responses to serotonin in LAD at DES edges were significantly suppressed in the LIPUS group compared with the sham group. Furthermore, lymph transport speed in vivo was significantly faster in the LIPUS group than in the sham group. Histological analysis at DES edges showed that inflammatory changes and Rho-kinase activity were significantly suppressed in the LIPUS group, associated with eNOS up-regulation and enhanced lymph-angiogenesis. Conclusions These results suggest that our non-invasive LIPUS therapy is useful to treat coronary functional abnormalities caused by coronary adventitial inflammation, indicating its potential for the novel and safe therapeutic approach of coronary artery disease.

A novel therapeutic approach for coronary inflammation and lymphatic vessels using non-invasive low-intensity pulsed ultrasound in a porcine model with DES-induced coronary hyperconstricting responses

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T Watanabe ◽  
Y Matsumoto ◽  
H Amamizu ◽  
S Morosawa ◽  
K Ohyama ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Therapeutic Approach ◽  
Sham Group ◽  
Lymphatic Vessels ◽  
Vasa Vasorum ◽  
Pulsed Ultrasound ◽  
Low Intensity Pulsed Ultrasound ◽  
Non Invasive ◽  
Low Intensity

Abstract Background The coronary adventitia harbors lymphatic vessels (LVs). We previously demonstrated that coronary adventitial inflammation and LV dysfunction play important roles in the pathogenesis of coronary artery spasm, including drug-eluting stent (DES)-induced coronary hyperconstricting responses, in pigs and humans. However, a direct therapeutic approach to the coronary adventitia remains to be developed. Purpose In this study, we aimed to examine whether our novel and non-invasive therapy with low-intensity pulsed ultrasound (LIPUS) ameliorates DES-induced coronary hyperconstricting responses, and if so, what mechanisms are involved. Methods An everolimus-eluting stent (EES) was implanted into the left anterior descending (LAD) coronary artery in normal male pigs. They were randomly assigned to the LIPUS or the sham therapy groups. After EES implantation, in the LIPUS group, LIPUS (32 cycles, 193 mW/cm2) was applied to the heart at 3 different levels (proximal and distal stent edges and middle portion of the stent) through X-ray fluoroscopy for 20 min at each level for every other day for 2 weeks (6 days in total) (Fig. 1A, B). The sham therapy group was treated in the same manner but without LIPUS. At 4 weeks after the procedure, we performed coronary angiography to examine coronary vasoconstricting responses to intracoronary serotonin in vivo. Finally, stented coronary vessels were harvested for immunohistochemistry of vasa vasorum (vWF), LVs (LYVE-1), vascular inflammation (CD68-positive macrophages and IL-1β expression), vascular endothelial growth factor A (VEGF-A, angiogenesis marker), VEGF-C and VEGF receptor 3 (VEGFR3, lymphangiogenesis markers). Results Coronary vasoconstricting responses to intracoronary serotonin at the DES edges in the LAD were significantly enhanced in the sham group but were significantly suppressed in the LIPUS group, while those responses were comparable at the non-DES implanted left circumflex (LCx) coronary artery between the 2 groups (Fig. 1C, D). In addition, in vivo lymph transport speed was significantly faster in the LIPUS group than in the sham group (Fig. 1E–G). In histological analysis, the number of LVs was significantly increased in the LIPUS group compared with the sham group, whereas those of CD68 and IL-1β expressions were significantly reduced in the LIPUS group compared with the sham group. In contrast, the density of vasa vasorum was comparable between the 2 groups. Mechanistically, the extents of VEGF-C and VEGFR3 expressions were increased in the LIPUS group, whereas that of VEGF-A was comparable between the 2 groups (Fig. 1G–K). Importantly, there were significant correlations among the LV-related changes and enhanced coronary vasoconstricting responses. Conclusion These results provide the first evidence that the LIPUS therapy ameliorates DES-induced coronary hyperconstricting responses in pigs in vivo through structural and functional alterations of LVs (Fig. 1L). Figure 1 Funding Acknowledgement Type of funding source: None

scholarly journals Osteocytes as main responders to low-intensity pulsed ultrasound treatment during fracture healing

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tatsuya Shimizu ◽  
Naomasa Fujita ◽  
Kiyomi Tsuji-Tamura ◽  
Yoshimasa Kitagawa ◽  
Toshiaki Fujisawa ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Transcriptional Control ◽  
Target Genes ◽  
Pulsed Ultrasound ◽  
Activated T Cells ◽  
In Vivo Models ◽  
Low Intensity Pulsed Ultrasound ◽  
Low Intensity ◽  
Ultrasound Stimulation

AbstractUltrasound stimulation is a type of mechanical stress, and low-intensity pulsed ultrasound (LIPUS) devices have been used clinically to promote fracture healing. However, it remains unclear which skeletal cells, in particular osteocytes or osteoblasts, primarily respond to LIPUS stimulation and how they contribute to fracture healing. To examine this, we utilized medaka, whose bone lacks osteocytes, and zebrafish, whose bone has osteocytes, as in vivo models. Fracture healing was accelerated by ultrasound stimulation in zebrafish, but not in medaka. To examine the molecular events induced by LIPUS stimulation in osteocytes, we performed RNA sequencing of a murine osteocytic cell line exposed to LIPUS. 179 genes reacted to LIPUS stimulation, and functional cluster analysis identified among them several molecular signatures related to immunity, secretion, and transcription. Notably, most of the isolated transcription-related genes were also modulated by LIPUS in vivo in zebrafish. However, expression levels of early growth response protein 1 and 2 (Egr1, 2), JunB, forkhead box Q1 (FoxQ1), and nuclear factor of activated T cells c1 (NFATc1) were not altered by LIPUS in medaka, suggesting that these genes are key transcriptional regulators of LIPUS-dependent fracture healing via osteocytes. We therefore show that bone-embedded osteocytes are necessary for LIPUS-induced promotion of fracture healing via transcriptional control of target genes, which presumably activates neighboring cells involved in fracture healing processes.

scholarly journals Low-Intensity Pulsed Ultrasound Promotes Autophagy-Mediated Migration of Mesenchymal Stem Cells and Cartilage Repair

2021 ◽  
Vol 30 ◽  
pp. 096368972098614
Author(s):  
Peng Xia ◽  
Xinwei Wang ◽  
Qi Wang ◽  
Xiaoju Wang ◽  
Qiang Lin ◽  
...  
Keyword(s):  
Cartilage Repair ◽  
Matrix Protein ◽  
Extracellular Matrix Protein ◽  
Histopathological Analysis ◽  
Pulsed Ultrasound ◽  
Low Intensity Pulsed Ultrasound ◽  
Low Intensity ◽  
Autophagy Inhibitor

Mesenchymal stem cell (MSC) migration is promoted by low-intensity pulsed ultrasound (LIPUS), but its mechanism is unclear. Since autophagy is known to regulate cell migration, our study aimed to investigate if LIPUS promotes the migration of MSCs via autophagy regulation. We also aimed to investigate the effects of intra-articular injection of MSCs following LIPUS stimulation on osteoarthritis (OA) cartilage. For the in vitro study, rat bone marrow-derived MSCs were treated with an autophagy inhibitor or agonist, and then they were stimulated by LIPUS. Migration of MSCs was detected by transwell migration assays, and stromal cell-derived factor-1 (SDF-1) and C-X-C chemokine receptor type 4 (CXCR4) protein levels were quantified. For the in vivo study, a rat knee OA model was generated and treated with LIPUS after an intra-articular injection of MSCs with autophagy inhibitor added. The cartilage repair was assessed by histopathological analysis and extracellular matrix protein expression. The in vitro results suggest that LIPUS increased the expression of SDF-1 and CXCR4, and it promoted MSC migration. These effects were inhibited and enhanced by autophagy inhibitor and agonist, respectively. The in vivo results demonstrate that LIPUS significantly enhanced the cartilage repair effects of MSCs on OA, but these effects were blocked by autophagy inhibitor. Our results suggest that the migration of MSCs was enhanced by LIPUS through the activation autophagy, and LIPUS improved the protective effect of MSCs on OA cartilage via autophagy regulation.

Low-Intensity Pulsed Ultrasound (LIPUS) May Prevent Polyethylene Induced Periprosthetic Osteolysis In Vivo

2012 ◽  
Vol 38 (2) ◽  
pp. 238-246 ◽  
Author(s):  
Xiang Zhao ◽  
Xun-Zi Cai ◽  
Zhong-Li Shi ◽  
Fang-Bing Zhu ◽  
Gang-Sheng Zhao ◽  
...  
Keyword(s):  
Pulsed Ultrasound ◽  
Periprosthetic Osteolysis ◽  
Low Intensity Pulsed Ultrasound ◽  
Low Intensity

scholarly journals 174 THE EFFECT OF LOW-INTENSITY PULSED ULTRASOUND FOR SACFFOLD-FREE CHONDROCYTE PLATE IN VITRO AND IN VIVO

2009 ◽  
Vol 17 ◽  
pp. S102-S103
Author(s):  
K. Uenaka ◽  
S. Imai ◽  
S. Shioji ◽  
K. Kumagai ◽  
N. Okumura ◽  
...  
Keyword(s):  
Pulsed Ultrasound ◽  
Low Intensity Pulsed Ultrasound ◽  
Low Intensity

scholarly journals Low Intensity Pulsed Ultrasound for Bone Tissue Engineering

Micromachines ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1488
Author(s):  
Colleen McCarthy ◽  
Gulden Camci-Unal
Keyword(s):  
Bone Formation ◽  
Bone Tissue ◽  
Mechanical Stimulation ◽  
Synergistic Effects ◽  
In Vivo Studies ◽  
Pulsed Ultrasound ◽  
Low Intensity Pulsed Ultrasound ◽  
Low Intensity

As explained by Wolff’s law and the mechanostat hypothesis, mechanical stimulation can be used to promote bone formation. Low intensity pulsed ultrasound (LIPUS) is a source of mechanical stimulation that can activate the integrin/phosphatidylinositol 3-OH kinase/Akt pathway and upregulate osteogenic proteins through the production of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2). This paper analyzes the results of in vitro and in vivo studies that have evaluated the effects of LIPUS on cell behavior within three-dimensional (3D) titanium, ceramic, and hydrogel scaffolds. We focus specifically on cell morphology and attachment, cell proliferation and viability, osteogenic differentiation, mineralization, bone volume, and osseointegration. As shown by upregulated levels of alkaline phosphatase and osteocalcin, increased mineral deposition, improved cell ingrowth, greater scaffold pore occupancy by bone tissue, and superior vascularization, LIPUS generally has a positive effect and promotes bone formation within engineered scaffolds. Additionally, LIPUS can have synergistic effects by producing the piezoelectric effect and enhancing the benefits of 3D hydrogel encapsulation, growth factor delivery, and scaffold modification. Additional research should be conducted to optimize the ultrasound parameters and evaluate the effects of LIPUS with other types of scaffold materials and cell types.

A influência da irradiação ultrassônica de baixa intensidade em cultura de células fibroblásticas

2015 ◽  
Vol 13 ◽  
pp. 306
Author(s):  
Larissa Dragonetti Bertin ◽  
Deise Aparecida Almeida Pires-Oliveira ◽  
Priscila Daniela Oliveira ◽  
Juliana Almeida Serpeloni ◽  
Stheace Kelly Fernandes Szezerbaty ◽  
...  
Keyword(s):  
Duty Cycle ◽  
Healing Process ◽  
Control Group ◽  
Mitochondrial Activity ◽  
Fibroblast Cells ◽  
Pulse Regime ◽  
Pulsed Ultrasound ◽  
Low Intensity Pulsed Ultrasound ◽  
Low Intensity

Introduction: In vitro and in vivo put in evidence that the Low Intensity Pulsed Ultrasound therapy exerts a significant influence on cell function (cytoskeleton organization, stimulation of mitochondrial activity, ATP levels and plasma membrane). Objective: This study will analyze the radiation of low intensity pulsed ultrasound in fibroblast cells L 929. Method: In this study are presented the data from each exposure group average and standard deviation in each moment of evaluation (24 hours, 48 hours and 72 hours). The control group (received no radiation), 0.2 W/cm2 with 10% pulse regime (1: 9 duty cycle), 0.2 W / cm2 with 20% pulse regime (2: 8 cycle work), 0.4 W/cm2 with pulse scheme 10% (1: 9 duty cycle), 0.4 W/cm2 with pulse scheme 20% (2: 8 duty cycle). The analyzes will be performed through optical microscopy, MTT method 3 - (4,5-dimethylthiazol-2-yl) -2,5 diphenyl tetrazolium bromide, within the incubation times of 24, 48 and 72 hours. Results: Given the above study, the results presented in this project will be directed to increase the stimulation process and proliferation of fibroblast cells from the pulsed ultrasonic irradiation of low intensity, correlating with the healing process, neovascularization and repair. Conclusion: Therefore, the study of the effect of ultrasound from cell culture provides us with a simple and informative model on the significant aspects of the use of physical therapy in vivo system.

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