Cardiac regenerative therapy using semaphorin 3A for failing myocardium

• Project/Area Number: 17K16025
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Nihon University
• Principal Investigator: KUROKAWA Sayaka 日本大学, 医学部, 助教 (60439130)
• Project Period (FY): 2017-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: セマフォリン3A / イソプロテレノール / 心筋リモデリング / 電気的リモデリング / 逆リモデリング / セマフォリン３A / 循環器 / 心筋 / 不整脈 / 心不全

Outline of Final Research Achievements

This study was conducted to validate the methodology for suppressing arrhythmias and heart failure by intravenous administration of the embryonic protein regulator semaphorin 3A (Sema3A) in an isoproterenol (ISP)-induced failing myocardium model, and to establish a new therapeutic concept using Sema3A. Additionally, the study demonstrated that Sema3A may inhibit the excessive distribution of sympathetic nerves in failing myocardium, contributing to alleviating myocardial tissue damage, maintaining left ventricular contractility, and suppressing arrhythmias. The results of this study have been presented at scientific conferences and published as a research article.

Academic Significance and Societal Importance of the Research Achievements

本研究によりSema3Aが不全心筋モデルにおける病的変化を改善させる逆リモデリング効果を持つことが示された。交感神経系の過負荷が病態形成に関与する心不全やカテコラミン心筋症などの治療にSema3Aが応用できる可能性を示唆する結果が得られたことには大いに意義がある。
一方、本研究はISP負荷不全心筋モデルマウスという特定の条件下でのSema3Aの効果を検討したものであり、ヒトの心不全や心筋症の治療に臨床応用するには今回得られたデータのみでは十分ではない。今後、ヒトの心疾患におけるSema3Aの役割や治療効果および安全性についてさらなる検討を要する。

Research Products

• [Journal Article] Intravenous semaphorin 3A administration maintains cardiac contractility and improves electrical remodeling in a mouse model of isoproterenol-induced heart failure. (2023)
  • Author(s): Kurokawa S, Kashimoto M, Hagikura K, Shimodai-Yamada S, Otsuka N, Wakamatsu Y, Nagashima K, Matsumoto T, Hao H, Okumura Y.
  • Journal Title: International Heart Journal Volume: 64
  • Peer Reviewed / Open Access
• [Presentation] Intravenous Semaphorin 3A Maintains Contractility and Improves Electrical Remodeling in Isoproterenol-Induced Myocardial Failure in Mice (2022)
  • Author(s): Sayaka Kurokawa
  • Organizer: 第86 回日本循環器学会学術集会(JCS2022)
  • Int'l Joint Research
• [Presentation] Intravenous Administration of Semaphorin 3A Improves Electrical Remodeling and Heart Failure to Regulate Catecholamine Overload (2021)
  • Author(s): Sayaka Kurokawa
  • Organizer: Heart Rhythm 2021
  • Int'l Joint Research