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

Tasuku Watanabe, Yasuharu Matsumoto, Kensuke Nishimiya, Tomohiko Shindo, Hirokazu Amamizu, Jun Sugisawa, Satoshi Tsuchiya, Koichi Sato, Susumu Morosawa, Kazuma Ohyama, Tomomi Watanabe-Asaka, Moyuru Hayashi, Yoshiko Kawai, Jun Takahashi, Satoshi Yasuda, Hiroaki Shimokawa

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article numbere0257175
JournalPloS one
Volume16
Issue number9 September
DOIs
Publication statusPublished - 2021 Sep

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'Low-intensity pulsed ultrasound therapy suppresses coronary adventitial inflammatory changes and hyperconstricting responses after coronary stent implantation in pigs in vivo'. Together they form a unique fingerprint.

Cite this