Regulatory mechanism of mitochondrial morphology by Nox4 and treatment for heart failure

• Project/Area Number: 15K19358
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Kyushu University (2016); Hokkaido University (2015)
• Principal Investigator: Matsushima Shoji 九州大学, 大学病院, 助教 (80552869)
• Co-Investigator(Renkei-kenkyūsha): TSUTSUI Hiroyuki 九州大学, 大学院医学研究院・循環器内科学, 教授 (70264017) ; KINUKAWA Shintaro 北海道大学, 大学院医学研究科・循環病態内科学, 講師 (60399871)
• Research Collaborator: MATSUMOTO Junichi 北海道大学, 大学院医学研究科・循環病態内科学, 大学院生 ; OKABE Kosuke 九州大学, 大学院医学研究院・循環器内科学, 大学院生 ; IKEDA Soichiro 九州大学, 大学院医学研究院・循環器内科学, 大学院生
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 心筋リモデリング / 心不全 / ミトコンドリア / 酸化ストレス

Outline of Final Research Achievements

In failing myocardium, mitochondrial size was decreased and number of mitochondria was incraesed. These changes were accompanited by a decrease in phosphorylation of Drp1, a inhibitor form of Drp1, and an increase in Mitofusin1. Treatment with angioteisinII (AngII) increased active form of Drp1 in cardiomyoctyes. GKT137831, a inhibitor of Nox4, inhibited AngII-induced activation of Drp1. These results suggest that Nox4 is a regulator of Drp1 and involved in mitochondrial dynamics in cardiomyocytes.

Research Products

• [Journal Article] Tyrosine kinase FYN negatively regulates NOX4 in cardiac remodeling. (2016)
  • Author(s): Matsushima S, Kuroda J, Zhai P, Liu T, Ikeda S, Nagarajan N, Oka S, Yokota T, Kinugawa S, Hsu C, Li H , Tsutsui H, Sadoshima J.
  • Journal Title: Journal of Clinical Investigation Volume: 126 Issue: 9 Pages: 3403-3416
  • DOI: 10.1172/jci85624
  • NAID: 120006809287
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] miR-206 Mediates YAP-Induced Cardiac Hypertrophy and Survival (2015)
  • Author(s): Yang Y, Del Re DP, Nakano N, Sciarretta S, Zhai P, Park J, Sayed D, Shirakabe A, Matsushima S, Park Y, Tian B, Abdellatif M, Sadoshima J.
  • Journal Title: Circulation Research Volume: 117 Issue: 10 Pages: 835-845
  • DOI: 10.1161/circresaha.115.306624
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Sesamin prevents decline in exercise capacity and impairment of skeletal muscle mitochondrial function in mice with high-fat diet-induced diabetes (2015)
  • Author(s): Takada S, Kinugawa S, Matsushima S, Takemoto D, Furihata T, Mizushima W, Fukushima A, Yokota T, Ono Y, Shibata H, Okita K, Tsutsui H
  • Journal Title: Exp Physiol Volume: 100 Issue: 11 Pages: 1319-30
  • DOI: 10.1113/ep085251
  • Peer Reviewed / Open Access
• [Journal Article] The role of sirtuins in cardiac disease. (2015)
  • Author(s): Matsushima S, Sadoshima J.
  • Journal Title: Am J Physiol Heart Circ Physiol. Volume: 309 Issue: 9 Pages: H1375-H1389
  • DOI: 10.1152/ajpheart.00053.2015
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Tyrosine kinase FYN negatively regulates NOX4 in cardiac remodeling (2017)
  • Author(s): Matsushima S
  • Organizer: 第81回日本循環器学会学術集会
  • Place of Presentation: 金沢
  • Year and Date: 2017-03-17
  • Invited
• [Presentation] 心不全治療ターゲットとしてのミトコンドリア (2016)
  • Author(s): Matsushima S
  • Organizer: 第20回日本心不全学会
  • Place of Presentation: 札幌
  • Year and Date: 2016-10-08
  • Invited
• [Presentation] Fyn is a Sensor and Regulator of Nox4-derived ROS in the Heart (2015)
  • Author(s): Matsushima S
  • Organizer: Cardiovascular and Metabolic Week 2015
  • Place of Presentation: 神戸国際会議場, 兵庫県神戸
  • Year and Date: 2015-12-11
• [Presentation] 心筋リモデリング・リバースリモデリングにおける酸化ストレスの役割 (2015)
  • Author(s): Matsushima S
  • Organizer: Cardiovascular and Metabolic Week 2015
  • Place of Presentation: 神戸国際会議場, 兵庫県神戸
  • Year and Date: 2015-12-10
  • Invited
• [Presentation] The role of NADPH oxidase 4 in cardiovascular disease (2015)
  • Author(s): Matsushima S
  • Organizer: Biochemistry and Molecular Biology 2015
  • Place of Presentation: 神戸国際会議場, 兵庫県神戸
  • Year and Date: 2015-12-02
  • Int'l Joint Research
• [Book] 日本臨床 最新冠動脈疾患学下 (2016)
  • Author(s): 松島 将士、筒井裕之
  • Total Pages: 5
  • Publisher: 日本臨床社
• [Book] 血圧 (2016)
  • Author(s): 松島 将士、筒井裕之
  • Total Pages: 4
  • Publisher: 先端医学社
• [Book] 血圧 (2015)
  • Author(s): 松島 将士、筒井裕之
  • Total Pages: 70
  • Publisher: 先端医学社
• [Book] 循環器内科 (2015)
  • Author(s): 松島 将士、筒井裕之
  • Total Pages: 215
  • Publisher: 科学評論社
• [Book] 心不全患者に寄り添う包括的心臓リハビリテーションを極める (2015)
  • Author(s): 松島 将士
  • Total Pages: 168
  • Publisher: 文光堂