Novel heart failure pharmacotherapy that targets nuclear signaling pathway in cardiac myocytes

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09108
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• 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)
• Research Collaborator: MORIMOTO Tatsuya 静岡県立大学 ; SUNAGAWA Yoichi 静岡県立大学 ; KATANASAKA Yasufumi 静岡県立大学 ; MIYAZAKI Yusuke 静岡県立大学
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 循環器・高血圧 / シグナル伝達 / 薬学 / トランスレーショナルリサーチ

Outline of Final Research Achievements

Heart failure is a leading cause of cardiovascular death. During development and deterioration of heart failure, cardiomyocytes undergo maladaptive hypertrophy, accompanied by re-induction of the fetal gene program. The transcriptional coactivator p300, an intrinsic histone acetyltransferase (HAT), is an important factor involved in the regulation of gene expression during cardiomyocyte hypertrophy. The natural compound, curcumin, possesses p300-specific HAT inhibitory activity. Our previous study demonstrated that curcumin prevents the development of cardiac hypertrophy by inhibiting p300-HAT activity. Here, we showed that demethoxycurcumin and bisdemethoxycurcumin, other major curcuminoids isolated from Curcuma longa, inhibited p300-HAT activity and cardiomyocyte hypertrophy to almost the same extent as curcumin. Thus, structural differences among the three compounds may not be involved in the inhibitory effects on p300-HAT activity and cardiac hypertrophy.

Free Research Field

循環器