Development of Novel Biomarker to Predict Cardiovascular Diseases

2011 Fiscal Year Final Research Report

• Project/Area Number: 21590884
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Tohoku University
• Principal Investigator: FUKUMOTO Yoshihiro 東北大学, 大学院・医学系研究科, 准教授 (70363372)
• Co-Investigator(Kenkyū-buntansha): HIROAKI Shimokawa 東北大学, 大学院・医学系研究科, 教授 (00235681)
• Project Period (FY): 2009 – 2011
• Keywords: Rhoキナーゼ活性 / 慢性心不全 / 肺高血圧症 / 狭心症 / 急性冠症候群

Research Abstract

In the present study, we have examined Rho-kinase activity in organ and peripheral white blood cells in patients with pulmonary hypertension, stable angina pectoris, acute coronary syndrome(acute myocardial infarction, unstable angina), chronic heart failure(Stage C-D), and acute heart failure. These results indicate that Rho-kinase is systemically and locally activated in patients with various cardiovascular diseases, suggesting that inhibition of Rho-kinase could be a new therapeutic strategy for cardiovascular diseases.

Research Products

• [Journal Article] Prognostic impact of myocardial interstitial fibrosis in non-ischemic heart failure (2011)
  • Author(s): Aoki T, Fukumoto Y, Sugimura K, Oikawa M, Satoh K, Nakano M, Nakayama M, Shimokawa H
  • Journal Title: Circ J Volume: 75 Pages: 2605-13
  • Peer Reviewed
• [Journal Article] Intensive Intensive immunosuppressive therapy improves pulmonary hemodynamics and long-term prognosis in patients with pulmonary arterial hypertension associated with connective tissue disease (2011)
  • Author(s): Miyamichi-Yamamoto S, Fukumoto Y, Sugimura K, Ishii T, Satoh K, Miura Y, Tatebe S, Nochioka K, Aoki T, Do E Z, Shimokawa H
  • Journal Title: Circ J Volume: 75 Pages: 2668-74
  • Peer Reviewed
• [Journal Article] Double-blind and placebo-controlled study of the effectiveness and safety of extracorporeal cardiac shock wave therapy for severe angina pectoris (2010)
  • Author(s): Kikuchi Y, Ito K, Ito Y, Shiroto T, Tsuburaya R, Aizawa K, Hao K, Fukumoto Y, Takahashi J, Takeda M, Nakayama M, Yasuda S, Kuriyama S, Tsuji I, Shimokawa H
  • Journal Title: Circ J Volume: 74 Pages: 589-91
  • Peer Reviewed
• [Journal Article] Acute vasodilator effects of inhaled fasudil, a specific Rho-kinase inhibitor, in patients with pulmonary arterial hypertension (2010)
  • Author(s): Fujita H, Fukumoto Y, Saji K, Sugimura K, Demachi J, Nawata J, Shimokawa H
  • Journal Title: Heart Vessels Volume: 25 Pages: 144-9
  • Peer Reviewed
• [Journal Article] Optical coherence tomography as a novel diagnostic tool for distal type chronic thromboembolic pulmonary hypertension (2010)
  • Author(s): Tatebe S, Fukumoto Y, Sugimura K, Nakano M, Miyamichi S, Satoh K, Oikawa M, Shimokawa H
  • Journal Title: Circ J Volume: 74 Pages: 1742-4
  • Peer Reviewed
• [Journal Article] Cardiac shock wave therapy ameliorates left ventricular remodeling after myocardial ischemia-reperfusion injury in pigs in vivo (2010)
  • Author(s): Ito Y, Ito K, Shiroto T, Tsuburaya R, Yi GJ, Takeda M, Fukumoto Y, Yasuda S, Shimokawa H
  • Journal Title: Coron Artery Dis Volume: 21 Pages: 304-11
  • Peer Reviewed
• [Journal Article] Identification of new prognostic factors of pulmonary hypertension (2010)
  • Author(s): Miura Y, Fukumoto Y, Sugimura K, Oikawa M, Nakano M, Tatebe S, Miyamichi S, Satoh K, Shimokawa H
  • Journal Title: Circ J Volume: 74 Pages: 1965-71
  • Peer Reviewed
• [Journal Article] Prognostic effects of calcium channel blockers in patients with vasospastic angina (2010)
  • Author(s): Nishigaki K, Inoue Y, Yamanouchi Y, Fukumoto Y, Yasuda S, Sueda S, Urata H, Shimokawa H, Minatoguchi S
  • Journal Title: Circ J Volume: 74 Pages: 1943-50
  • Peer Reviewed
• [Journal Article] Prevalence and clinical implication of metabolic syndrome in chronic heart failure (2010)
  • Author(s): Miura Y, Fukumoto Y, Shiba N, Miura T, Shimada K, Iwama Y, Takagi A, Matsusaka H, Tsutsumi T, Yamada A, Kinugawa S, Asakura M, Okamatsu S, Tsutsui H, Daida H, Matsuzaki M, Tomoike H, Shimokawa H
  • Journal Title: Circ J Volume: 74 Pages: 2612-21
  • Peer Reviewed
• [Journal Article] OX40 ligand plays an important role in the development of atherosclerosis through vasa vasorum neovascularization (2010)
  • Author(s): Nakano M, Fukumoto Y, Satoh K, Ito Y, Kagaya Y, Ishii N, Sugamura K, Shimokawa H
  • Journal Title: Cardiovasc Res Volume: 88 Pages: 539-46
  • Peer Reviewed
• [Journal Article] Hypertension promotes phosphorylation of focal adhesion kinase and proline-rich tyrosine kinase 2 in rats-Implication for the pathogenesis of hypertensive vascular disease- (2010)
  • Author(s): Sugimura K, Fukumoto Y, Nawata J, Wang H, Onoue N, Tada T, Shirato K, Shimokawa H
  • Journal Title: Tohoku J Exp Med Volume: 222 Pages: 201-210
  • Peer Reviewed
• [Journal Article] Statin ameliorates hypoxia-induced pulmonary hypertension associated with down-regulated stromal cell-derived factor-1 (2009)
  • Author(s): Satoh K, Fukumoto Y, Nakano M, Sugimura K, Nawata J, Demachi J, Karibe A, Kagaya Y, Ishii N, Sugamura K, Shimokawa H
  • Journal Title: Cardiovasc Res Volume: 81 Pages: 226-34
  • Peer Reviewed
• [Journal Article] Importance of Rac1 signaling pathway inhibition in the pleiotropic effects of HMG-CoA reductase inhibitors (2009)
  • Author(s): Rashid M, Tawara S, Fukumoto Y, Seto M, Yano K, Shimokawa H
  • Journal Title: Circ J Volume: 73 Pages: 361-70
  • Peer Reviewed
• [Journal Article] Diabetes mellitus accelerates left ventricular diastolic dysfunction through activation of the renin-angiotensin system in hypertensive rats (2009)
  • Author(s): Fukui S, Fukumoto Y, Suzuki J, Saji K, Nawata J, Shinozaki T, Kagaya Y, Watanabe J, Shimokawa H
  • Journal Title: Hypertens Res Volume: 32 Pages: 472-80
  • Peer Reviewed
• [Journal Article] Evidence for Rho-Kinase Activation in Patients With Pulmonary Arterial Hypertension (2009)
  • Author(s): Do E Z, Fukumoto Y, Takaki A, Tawara S, Ohashi J, Nakano M, Tada T, Saji K, Sugimura K, Fujita H, Hoshikawa Y, Nawata J, Kondo T, Shimokawa H
  • Journal Title: Circ J Volume: 73 Pages: 1731-9
  • Peer Reviewed
• [Journal Article] SLCO4C1 transporter eliminates uremic toxins and attenuates hypertension and renal inflammation (2009)
  • Author(s): Toyohara T, Suzuki T, Morimoto R, Akiyama Y, Souma T, Shiwaku HO, Takeuchi Y, Mishima E, Abe M, Tanemoto M, Masuda S, Kawano H, Maemura K, Nakayama M, Sato H, Mikkaichi T, Yamaguchi H, Fukui S, Fukumoto Y, Shimokawa H, Inui K, Terasaki T, Goto J, Ito S, Hishinuma T, Rubera I, Tauc M, Fujii-Kuriyama Y, Yabuuchi H, Moriyama Y, Soga T, Abe T
  • Journal Title: J Am Soc Nephrol Volume: 20 Pages: 2546-55
  • Peer Reviewed
• [Presentation] Rho-kinase Activity in Circulating Leukocytes as a Novel Biomarker in Patients with Chronic Heart Failure (2012)
  • Author(s): YZhulanqiqige Do. e, Yoshihiro Fukumoto, Koichiro Sugimura, Yutaka Miura, Saori Yamamoto, Shunsuke Tatebe, Tatsuo Aoki, Kotaro Nochioka, Kimio Satoh, Hiroaki Shimokawa
  • Organizer: 第76回日本循環器学会総会・学術集会
  • Place of Presentation: 京都
  • Year and Date: 2012-03-17
• [Presentation] (東北大学病院循環器内科)心不全ガイドラインを見直す (2011)
  • Author(s): 福本義弘
  • Organizer: 第15回日本心不全学会学術集会
  • Place of Presentation: 鹿児島
  • Year and Date: 2011-10-14
• [Presentation] (東北大学病院循環器内科)心不全に期待される新薬:ファスジル(Rhoキナーゼ阻害薬) (2010)
  • Author(s): 福本義弘
  • Organizer: 第14回日本心不全学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 20101007-09
• [Presentation] (東北大学病院循環器内科)三浦俊郎、松崎益徳(山口大学)島田和典、岩間義孝、高木篤俊、代田浩之(順天堂大学)朝倉正紀、友池仁暢(国立循環器病センター)堤孝樹、山田明(飯塚病院)絹川真太郎、筒井裕之(北海道大学)わが国の慢性心不全の成因における糖尿病の意義 (2010)
  • Author(s): 福本義弘、三浦裕、福井重文、柴信行、下川宏明
  • Organizer: 第58回日本心臓病学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2010-09-18
• [Presentation] (東北大学病院循環器内科)肺高血圧症における新たな分子治療標的 : Rhoキナーゼの重要性 (2010)
  • Author(s): 福本義弘下川宏明
  • Organizer: 第58回日本心臓病学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2010-09-17
• [Presentation] Current Status and Future Perspectives of Diastolic Heart Failure in Japan-Rho-kinase as a Possible Therapeutic Target- (2010)
  • Author(s): Yoshihiro Fukumoto, Yutaka Miura, Shigefumi Fukui, Tatsuo Aoki, Toshiro Miura, Masunori Matsuzaki, Kazunori Shimada, Yoshitaka Iwama, atsutoshi Takagi, Hiroyuki Daida, Takaki Tsutsumi, Akira Yamada, Shintaro Kinugawa, Hiroyuki Tsutsui, Masanori Asakura, Hitonobu Tomoike, 1Nobuyuki Shiba, Hiroaki Shimokawa
  • Organizer: 第74回日本循環器学会総会・学術集会
  • Place of Presentation: 京都
  • Year and Date: 2010-03-05
• [Book] 心疾患動物モデル。完全版マウス・ラット疾患モデル活用ハンドブック (2011)
  • Author(s): 珠蘭其其格、福本義弘
  • Total Pages: 320-333
  • Publisher: 羊土社
• [Book] 肺高血圧症に対するRhoキナーゼ阻害薬の治療効果 (2011)
  • Author(s): 福本義弘、下川宏明
  • Total Pages: 263-269
  • Publisher: 中外医学社
• [Book] 心不全日常診療Q & A (2011)
  • Author(s): 青木竜男、杉村宏一郎、福本義弘
  • Total Pages: 264-266
  • Publisher: 南山堂
• [Book] 薬効群別副作用脂質異常症治療薬, 医薬品副作用ハンドブック第2版 (2010)
  • Author(s): 福本義弘、下川宏明
  • Total Pages: 97-102
  • Publisher: 日本臨床社
• [Book] 5章重症心不全を予防する10.メタボリックシンドロームを治す。重症心不全の予防と治療 (2009)
  • Author(s): 福本義弘、下川宏明
  • Total Pages: 377-380
  • Publisher: 中外医学社
• [Remarks]
  • URL: http://www.cardio.med.tohoku.ac.jp/class/research/blood02.html