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

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 t...

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Autores principales: Watanabe, Tasuku, Matsumoto, Yasuharu, Nishimiya, Kensuke, Shindo, Tomohiko, Amamizu, Hirokazu, Sugisawa, Jun, Tsuchiya, Satoshi, Sato, Koichi, Morosawa, Susumu, Ohyama, Kazuma, Watanabe-Asaka, Tomomi, Hayashi, Moyuru, Kawai, Yoshiko, Takahashi, Jun, Yasuda, Satoshi, Shimokawa, Hiroaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8437271/
https://www.ncbi.nlm.nih.gov/pubmed/34516572
http://dx.doi.org/10.1371/journal.pone.0257175
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author Watanabe, Tasuku
Matsumoto, Yasuharu
Nishimiya, Kensuke
Shindo, Tomohiko
Amamizu, Hirokazu
Sugisawa, Jun
Tsuchiya, Satoshi
Sato, Koichi
Morosawa, Susumu
Ohyama, Kazuma
Watanabe-Asaka, Tomomi
Hayashi, Moyuru
Kawai, Yoshiko
Takahashi, Jun
Yasuda, Satoshi
Shimokawa, Hiroaki
author_facet Watanabe, Tasuku
Matsumoto, Yasuharu
Nishimiya, Kensuke
Shindo, Tomohiko
Amamizu, Hirokazu
Sugisawa, Jun
Tsuchiya, Satoshi
Sato, Koichi
Morosawa, Susumu
Ohyama, Kazuma
Watanabe-Asaka, Tomomi
Hayashi, Moyuru
Kawai, Yoshiko
Takahashi, Jun
Yasuda, Satoshi
Shimokawa, Hiroaki
author_sort Watanabe, Tasuku
collection PubMed
description 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/cm(2)) 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.
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spelling pubmed-84372712021-09-14 Low-intensity pulsed ultrasound therapy suppresses coronary adventitial inflammatory changes and hyperconstricting responses after coronary stent implantation in pigs in vivo Watanabe, Tasuku Matsumoto, Yasuharu Nishimiya, Kensuke Shindo, Tomohiko Amamizu, Hirokazu Sugisawa, Jun Tsuchiya, Satoshi Sato, Koichi Morosawa, Susumu Ohyama, Kazuma Watanabe-Asaka, Tomomi Hayashi, Moyuru Kawai, Yoshiko Takahashi, Jun Yasuda, Satoshi Shimokawa, Hiroaki PLoS One Research Article 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/cm(2)) 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. Public Library of Science 2021-09-13 /pmc/articles/PMC8437271/ /pubmed/34516572 http://dx.doi.org/10.1371/journal.pone.0257175 Text en © 2021 Watanabe et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Watanabe, Tasuku
Matsumoto, Yasuharu
Nishimiya, Kensuke
Shindo, Tomohiko
Amamizu, Hirokazu
Sugisawa, Jun
Tsuchiya, Satoshi
Sato, Koichi
Morosawa, Susumu
Ohyama, Kazuma
Watanabe-Asaka, Tomomi
Hayashi, Moyuru
Kawai, Yoshiko
Takahashi, Jun
Yasuda, Satoshi
Shimokawa, Hiroaki
Low-intensity pulsed ultrasound therapy suppresses coronary adventitial inflammatory changes and hyperconstricting responses after coronary stent implantation in pigs in vivo
title Low-intensity pulsed ultrasound therapy suppresses coronary adventitial inflammatory changes and hyperconstricting responses after coronary stent implantation in pigs in vivo
title_full Low-intensity pulsed ultrasound therapy suppresses coronary adventitial inflammatory changes and hyperconstricting responses after coronary stent implantation in pigs in vivo
title_fullStr Low-intensity pulsed ultrasound therapy suppresses coronary adventitial inflammatory changes and hyperconstricting responses after coronary stent implantation in pigs in vivo
title_full_unstemmed Low-intensity pulsed ultrasound therapy suppresses coronary adventitial inflammatory changes and hyperconstricting responses after coronary stent implantation in pigs in vivo
title_short Low-intensity pulsed ultrasound therapy suppresses coronary adventitial inflammatory changes and hyperconstricting responses after coronary stent implantation in pigs in vivo
title_sort low-intensity pulsed ultrasound therapy suppresses coronary adventitial inflammatory changes and hyperconstricting responses after coronary stent implantation in pigs in vivo
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8437271/
https://www.ncbi.nlm.nih.gov/pubmed/34516572
http://dx.doi.org/10.1371/journal.pone.0257175
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