Translational Research toward novel pharmacotherapy for left ventricular diastolic dysfunction targeting intranuclear signal transduction in cardiomyocytes

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08069
• 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: Department of Clinical Research, National Hospital Organization Kyoto Medical Center
• Principal Investigator: Hasegawa Koji 独立行政法人国立病院機構(京都医療センター臨床研究センター), 展開医療研究部, 研究部長 (50283594)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 心不全 / 転写調節因子 / 薬物療法 / 情報伝達 / 心筋細胞

Outline of Final Research Achievements

With the arrival of a super-aging society, patients of heart failure with preserved ejection fraction are increasing in number, and it is an urgent necessity to establish a new treatment strategy to suppress the onset of heart failure. For the past 20 years, we have been energetically conducting medical research to elucidate the nuclear signal transduction mechanism in cardiac myocytes. We found that a main component of turmeric, curcumin, that specifically inhibits p300 HAT activity, suppresses the onset and exacerbation of heart failure. A double-blind randomized controlled clinical trial showed that high-absorption curcumin significantly suppressed the rise in blood BNP levels in patients with hypertensive heart disease.

Free Research Field

循環器内科学　予防医学　薬物療法学

Academic Significance and Societal Importance of the Research Achievements

心不全は高血圧性心疾患、虚血性心疾患などすべての心疾患の共通最終像であるが、年齢と共に心臓は拡張能が低下し、収縮能が正常でも運動耐容能低下や肺うっ血などの心不全を来す。特に収縮能の保たれた心不全(HFpEF)に対して心筋を特異的に標的とした有効な薬物はなく、SGLT2阻害薬の利尿作用・腎保護作用に頼るのみである。超高齢化社会の到来と共に HFpEF は急増しており、心不全の発症と進展を抑制する新たな治療法を確立することは社会的、医療経済的急務である。本研究では情報伝達解明から臨床現場へと着実に研究を進めてきた。