Research for new heart failure treatment targets by elucidating the pathogenic mechanism of Takotsubo syndrome

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08084
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Nara Medical University
• Principal Investigator: Onoue Kenji 奈良県立医科大学, 医学部, 講師 (90510173)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 急性心不全 / たこつぼ症候群 / カテコラミン心毒性

Outline of Final Research Achievements

The number of heart failure patients in Japan continues to increase, and more effective treatment methods are needed. Takotsubo syndrome (TTS), which develops acute heart failure, is a group of diseases characterized by a transient decrease in cardiac contractility, and cardiac sympathetic nervous system disorder due to acute catecholamine toxicity is thought to be the primary pathogenic mechanism.
In this study, we created mice with high expression of the sympathetic nervous system regulator GRK2, which increases with age, in the myocardium, induced TTS, and analyzed the effects on cardiac function and sympathetic nervous system molecules. When TTS was induced in wild-type and GRK2-high-expressing mice, the latter became more severe, and the production of reactive oxygen species was involved.
We want to continue our research so that the knowledge obtained in this study can be utilized for heart failure treatment.

Free Research Field

心不全

Academic Significance and Societal Importance of the Research Achievements

超高齢社会を迎える我が国において心不全患者数は増加の一途にあり、より効果的な治療法を探索することが喫緊の課題となっている。心不全患者では交感神経活性が亢進しており、カテコラミン濃度が高い患者ほど予後不良であるため交感神経活性が予後規定因子とされる。交感神経活性が強く関与する疾患として、急性心不全で発症するたこつぼ症候群(TTS)がある。本研究では交感神経系シグナル制御因子で加齢とともに増加が報告されているGRK2の過剰発現がTTSの病態を悪化させることが判明した。
本研究で得られた知見が心不全全般に認められるか検討する必要はあるが、新たな心不全治療の標的となる可能性がある。