Application of PRMT5 targeted pharmacological therapy for heart failure

• Project/Area Number: 16K18876
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: University of Shizuoka
• Principal Investigator: Katanasaka Yasufumi 静岡県立大学, 薬学部, 講師 (00583973)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: アルギニンメチル化酵素 / 心肥大 / 心不全 / エピジェネティクス / PRMT5 / p300 / ヒストン修飾 / GATA4 / 薬学

Outline of Final Research Achievements

We investigate the potential of heart failure therapy targeting PRMT5. Pressure overload-induced cardiac hypertrophy and heart failure are suppressed by treatment with PRMT5 inhibitor. PRMT5 enhances p300 histone acetyltransferase activity in heart. These results indicate that PRMT5 is a possible molecular target for heart failure therapy.

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、世界で初めてアルギニンメチル化酵素を標的とする心不全薬物療法の可能性を示した。これは学術的にはもちろん、いまだ十分とは言えない心不全薬物治療の新たな可能性を示しており、社会的意義も大きいと考える。

Research Products

• [Journal Article] CRISPR-Mediated Gene Editing to Assess the Roles of Tet2 and Dnmt3a in Clonal Hematopoiesis and Cardiovascular Disease (2018)
  • Author(s): Sano Soichi、Oshima Kosei、Wang Ying、Katanasaka Yasufumi、Sano Miho、Walsh Kenneth
  • Journal Title: Circulation Research Volume: 123 Issue: 3 Pages: 335-341
  • DOI: 10.1161/circresaha.118.313225
  • Peer Reviewed
• [Journal Article] Tet2-Mediated Clonal Hematopoiesis Accelerates Heart Failure Through a Mechanism Involving the IL-1β/NLRP3 Inflammasome (2018)
  • Author(s): Sano Soichi、Oshima Kosei、Wang Ying、MacLauchlan Susan、Katanasaka Yasufumi、Sano Miho、Zuriaga Maria A.、Yoshiyama Minoru、Goukassian David、Cooper Matthew A.、Fuster Jose、Walsh Kenneth
  • Journal Title: Journal of the American College of Cardiology Volume: 71 Issue: 8 Pages: 875-886
  • DOI: 10.1016/j.jacc.2017.12.037
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Tyrosine phosphorylation of RACK1 triggers cardiomyocyte hypertrophy by regulating the interaction between p300 and GATA4. (2016)
  • Author(s): Suzuki H, Katanasaka Y, Sunagawa Y, Miyazaki Y, Funamoto M, Wada H, Hasegawa K, Morimoto T.
  • Journal Title: Biochim Biophys Acta. Volume: 9 Issue: 9 Pages: 1544-1557
  • DOI: 10.1016/j.bbadis.2016.05.006
  • Peer Reviewed
• [Journal Article] Regulation of Cardiac Transcription Factor GATA4 by Post-Translational Modification in Cardiomyocyte Hypertrophy and Heart Failure (2016)
  • Author(s): Katanasaka Y, Suzuki H, Sunagawa Y, Hasegawa K and Morimoto T.
  • Journal Title: International Heart Journal Volume: 57 Issue: 6 Pages: 672-675
  • DOI: 10.1536/ihj.16-404
  • NAID: 130005172007
  • ISSN: 1349-2365, 1349-3299
  • Peer Reviewed
• [Presentation] アルギニンメチル化酵素PRMT5を標的とした心不全分子標的療法 (2018)
  • Author(s): 刀坂泰史, 佐藤光, 櫻井涼賀, 宮崎雄輔, 砂川陽一, 和田啓道, 長谷川浩二, 森本達也
  • Organizer: 日本薬学会第138年会
• [Presentation] Cardiac-specific PRMT5 overexpression accelerates pressure overload-induced cardiac hypertrophy and heart failure (2018)
  • Author(s): Yasufumi Katanasaka, Ryoga Sakurai, Yuya Hojo, Yusuke Tsutsui, Yusuke Miyazaki, Yoichi Sunagawa, Hiromichi Wada, Koji Hasegawa, Tatsuya Morimoto
  • Organizer: 第一回日本循環器学会基礎研究フォーラム
• [Presentation] 心血管疾患の分子病態解析と分子標的薬物治療への応用 (2016)
  • Author(s): 刀坂泰史
  • Organizer: 第62回日本薬学会東海支部 総会・大会
  • Place of Presentation: 愛知
  • Year and Date: 2016-07-09
  • Invited