Basic study to evaluate the effectiveness of low-intensity pulsed ultrasound therapy for heart failure due to diastolic dysfunction.

• Project/Area Number: 18K15877
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Tohoku University
• Principal Investigator: Shindo Tomohiko 東北大学, 大学病院, 助教 (80781294)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2018: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 心不全 / 超音波治療 / 低侵襲治療 / 介入研究 / 拡張障害 / eNOS / 低出力パルス波超音波 / 低侵襲性治療 / 血管新生療法

Outline of Final Research Achievements

In the db / db mice treated with LIPUS therapy, the decrease in the left ventricular diastolic function and the decrease in exercise tolerance were suppressed. In addition, hypertrophy and fibrosis of the myocardium were suppressed, activation of Ca2 + handling-related proteins in the myocardium, and accompanying improvement in relaxation characteristics at the myocardial tissue level were observed. Furthermore, in protein expression analysis by Western-blotting, phosphorylation of endothelial NO synthase (eNOS) was significantly increased, and the increased expression of soluble guanylate cyclase and protein kinase G (PKG), which are downstream molecules of eNOS, was confirmed.

Academic Significance and Societal Importance of the Research Achievements

HFpEFは今や最も一般的なタイプの心不全となっており、世界中で最も深刻な健康問題の1つとして位置づけられている。HFpEFを対象とした多くの臨床試験が行われてきたが、いまだその予後を改善するための効果的な治療法の確立には至っていない。その様な状況の中、LIPUSが、血管内皮に直接働きかけ、eNOS-NO-cGMP-PKG経路の活性化を介してHFpEFの病態を改善することを動物モデルで実証することができた。HFpEFに対する有効な薬物療法がない中、超音波による物理刺激という従来の薬物療法とは全く異なるアプローチがHFpEFに有効であることが確認されれば、医学的意義は極めて高いものと考えられる。

Research Products

• [Journal Article] Low-intensity pulsed ultrasound ameliorates cardiac diastolic dysfunction in mice-A possible novel therapy for HFpEF (2020)
  • Author(s): Monma Y, Shindo T, Eguchi K, Kurosawa R, Kagaya Y, Ikumi Y, Ichijo S, Nakata T, Miyata S, Matsumoto A, Sato H, Miura M, Kanai H, Shimokawa H
  • Journal Title: Cardiovasc Res Volume: Jul 19 Issue: 5 Pages: 1325-1338
  • DOI: 10.1093/cvr/cvaa221
  • Peer Reviewed / Open Access
• [Presentation] Low-intensity Pulsed Ultrasound Ameliorates Diastolic Cardiac Dysfunction in Mice (2019)
  • Author(s): Yuto Monma
  • Organizer: AHA2019 American Heart Association Scientific Sessions Meeting
• [Presentation] Low-intensity Pulsed Ultrasound Ameliorates Diastolic Cardiac Dysfunction in Mice (2019)
  • Author(s): 門間雄斗
  • Organizer: 第83回日本循環器学会