The novel therapy of pulmonary hypertension by preventing right heart failure

• Project/Area Number: 16K19409
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Yamaguchi University
• Principal Investigator: ONO Makoto 山口大学, 医学部附属病院, 診療助教(4日/週) (50650321)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: カルモジュリン / リアノジン受容体 / 肺高血圧 / Ca2+ ハンドリング / 肺動脈性肺高血圧 / 肺動脈性肺高血圧症 / 右室肥大

Outline of Final Research Achievements

PAH mice and Sham mice were orally administered the Ca leak inhibitor dantrolene, and the right ventricular pressure was measured, the cardiomyocyte size was measured, Ca transient observation, fixed and anti-CaM, anti-GRK 5, anti-HDAC 4, 5, anti Immunostaining was performed with antibodies of -p-HDAC 4, 5. As a result, oral administration of dantrolene did not affect pulmonary artery pressure. In the oral administration group of dantrolene, myocardial cell size was reduced and the hypertrophy was suppressed. Furthermore, reduction of RyR bound CaM was suppressed. From this, it was suggested that dantrolene inhibited the dissociation of CaM from RyR, thus suppressing hypertrophy.

Research Products

• [Journal Article] Strict sequential catheter ablation strategy targeting the pulmonary veins and superior vena cava for persistent atrial fibrillation (2018)
  • Author(s): Yoshiga Y, Shimizu A, Ueyama T, Ono M, Fukuda M, Fumimoto T, Ishiguchi H, Omuro T, Kobayashi S, Yano M.
  • Journal Title: Journal of Cardiology Volume: in press Pages: 128-134
  • DOI: 10.1016/j.jjcc.2018.01.004
  • Peer Reviewed
• [Journal Article] 2.Mutation-linked excessively tight interaction between the calmodulin-binding domain and c-terminal domain of the cardiac ryanodine receptor as a novel cause of catecholaminergic polymorphic ventricular tachycardia. (2018)
  • Author(s): Nishimura S, Yamamoto T, Nakamura Y, Kohno M, Hamada Y, Sufu Y, Fukui G, Nanno T, Ishiguchi H, Kato T, Xu X, Ono M, Oda T, Okuda S, Kobayashi S, Yano M.
  • Journal Title: Heart Rhythm Volume: 印刷中 Pages: 905-914
  • DOI: 10.1016/j.hrthm.2018.02.006
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Macroreentrant form of an adenosine 5′-triphosphate sensitive atrial tachycardia arising from the vicinity of the atrioventricular node involving the tricuspid and mitral annuli as its reentrant circuit (2017)
  • Author(s): Ueyama Takeshi、Shimizu Akihiko、Yoshiga Yasuhiro、Ono Makoto、Fumimoto Tomoko、Yano Masafumi
  • Journal Title: HeartRhythm Case Reports Volume: 3 Pages: 289-293
  • DOI: 10.1016/j.hrcr.2017.03.001
  • Peer Reviewed
• [Journal Article] Inferior J waves in patients with vasospastic angina might be a risk factor for ventricular fibrillation. (2017)
  • Author(s): Fumimoto T, Ueyama T, Shimizu A, Yoshiga Y, Ono M, Kato T, Ishiguchi H, Okamura T, Yamada J, Yano M.
  • Journal Title: J Cardiol Volume: 70 Pages: 271-277
  • DOI: 10.1016/j.jjcc.2016.12.003
  • Peer Reviewed
• [Journal Article] Correction of impaired calmodulin binding to RyR2 as a novel therapy for lethal arrhythmia in the pressure-overloaded heart failure (2017)
  • Author(s): Kato T, Yamamoto T, Nakamura Y, Nanno T, Fukui G, Sufu Y, Hamada Y, Maeda T, Nishimura S, Ishiguchi H, Murakami W, Fukuda M, Xu X, Hino A, Ono M, Oda T, Okuda S, Kobayashi S, Koseki N, Kyushiki H, Yano M.
  • Journal Title: Heart Rhythm. Volume: 14 Pages: 120-127
  • DOI: 10.1016/j.hrthm.2016.10.019
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Successful cryoballoon pulmonary vein isolation in a patient with situs inversus and dextrocardia (2016)
  • Author(s): Yoshiga Y, Shimizu A, Ueyama T, Ono M, Fumimoto T, Ishiguchi H, Yano M.
  • Journal Title: J Arrhythm Volume: 32 Pages: 493-496
  • Peer Reviewed