Role of Epac in cardiac fibrosis and its clinical application for heart failure

• Project/Area Number: 23591087
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Tsurumi University
• Principal Investigator: OKUMURA Satoshi 鶴見大学, 歯学部, 教授 (60233475)
• Co-Investigator(Kenkyū-buntansha): SATO Motohiko 愛知医科大学, 医学部, 教授 (40292122)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: シグナル伝達 / 循環器高血圧 / サイクリックAMP / 心不全 / 遺伝子改変マウス

Research Abstract

In order to examine the role of Epac1 (exchange protein directly activated by cyclic AMP) on cardiac fibrosis, chronic isoproterenol (ISO) infusion (60mg/kg/day for 7 days) was performed in Epac1-null mice (Epac1KO) and wild-type controls (WT). Cardiac fibrosis was significantly inhibited in Epac1KO, compared to WT. In order to examine the mechanism, we examined the role of Epac1 in the following 3 steps : Step-1) Production of collagen fiber Step-2) Cross-linking of collagen fiber by lysyl oxidase (LOX) Step-3) Degradation of collagen fiber by matrix mettaloproteinase (MMT). Our data in this study shows that cardiac fibrosis was reduced through the inhibition of step-3.

Research Products

• [Journal Article] Epac1-dependent phospholamban phosphorylation mediates the cardiac response to stresses (2014)
  • Author(s): Okumura S, Fujita T, Cai W, Jin M, Namekata I, Mototani Y, Jin H, Ohnuki Y, Tsuneoka Y, Kurotani R, Suita K, Kawakami Y, Hamaguchi S, Abe T, Kiyonari H, Tsunematsu T, Bai Y, Suzuki S, Hidaka Y, Umemera M, Ichikawa Y, Yokoyama U, Sato m, Ishikawa F, Izumi-Nakaseko H, Adachi-Akahane S, Tanaka H, Ishikawa Y
  • Journal Title: J Clin Invest Volume: 124 Pages: 2785-2801
  • Peer Reviewed
• [Journal Article] Protection of cardiomyocytes from the hypoxia-mediated injury by a peptide targeting the G-protein signaling 8 (2014)
  • Author(s): Sato M, Hiraoka M, Sakima M, Yamane Y, Fujita T, Okumura S, Ishikawa Y
  • Journal Title: PLoS One Volume: 14
  • Peer Reviewed
• [Journal Article] (2014)
  • Author(s): Sato I, Umemura M, Mitsudo K, Kioi M, Nakashima H, Iwai T, Feng X, Oda K, Miyajima A, Makino A, Iwai M, Fujita T, Yokoyama U, Okumura S, Sato M, Eguchi H, Tohnai I, Ishikawa Y
  • Journal Title: J Physiol Sci Volume: 64 Pages: 177-183
  • Peer Reviewed
• [Journal Article] Effects of the masticatory demand on the rat mandibular development (2014)
  • Author(s): Hichijo N, Kawai N, Mori H, Sano R, Ohnuki Y, Okumura S, langenbach GE, Tanaka E
  • Journal Title: J Oral Rehabil Volume: (in press)
  • Peer Reviewed
• [Journal Article] Epac1-dependent phosphorylamban phosphorylation mediates the cardiac response to stresses (2014)
  • Author(s): Okumura S et al.
  • Journal Title: J Clin Invest Volume: in press
  • Peer Reviewed
• [Journal Article] Protection of cardiomyocytes from the hypoxia-mediated injury by a peptide targeting the activator of G-protein signaling 8. (2014)
  • Author(s): Sato M, Hiraoka M, Suzuki H, Sakima M, Mamun, AA, Yamane Y, Fujita T, Yokoyama U, Okumura S, and Ishikawa Y.
  • Journal Title: PLoS ONE. Volume: 9 Issue: 3 Pages: e91980-e91980
  • DOI: 10.1371/journal.pone.0091980
  • Peer Reviewed / Open Access
• [Journal Article] Hyperthermia generated with ferucarbotran (Resovis®) in an alternating magnetic field enhances cisplatin-induced apoptosis of cultured human oral cancer cells. (2014)
  • Author(s): Sato I, Umemura M, Mitsudo K, Kioi M, Nakashima H, Iwai T Fujita T, Yokoyama U, Okumura S, Feng X, Ito K, Miyajima A, Makino A, Iwai M, Eguchi H, I wai T, and Ishikawa Y.
  • Journal Title: J. Physiol. Sci. Volume: 64 Issue: 3 Pages: 177-183
  • DOI: 10.1007/s12576-014-0309-8
  • Peer Reviewed / Open Access
• [Journal Article] Effects of the masticatory demand on the rat mandibular development (2014)
  • Author(s): Hichijo N, Okumura S et al
  • Journal Title: J Oral Rehabil Volume: in press Issue: 8 Pages: 581-587
  • DOI: 10.1111/joor.12171
  • Peer Reviewed
• [Journal Article] 咀嚼筋肥大刺激のミオシン重鎖のサブタイプスイッチングに与える効果 (2014)
  • Author(s): 奥村敏 他
  • Journal Title: 日本病態生理学会雑誌 Volume: in press
• [Journal Article] 全身の健康増進における口腔生理機能の重要性 (2014)
  • Author(s): 奥村敏 他
  • Journal Title: 日本生理学会雑誌 Volume: 76 Pages: 76-77
• [Journal Article] Effect of protein kinase A on the phosphorylation status and transverse stiffness of cardiac myofibrils (2013)
  • Author(s): Ohnuki Y, Yamada T, Mototani Y, Umeki D, Shiozawa K, Fujita T, Saeki Y, Okumura S
  • Journal Title: J Pharamacol Sci Volume: 123 Pages: 279-283
  • NAID: 130003382605
  • Peer Reviewed
• [Journal Article] Role of masseter muscleβ2-adrenergic signaling in regulation of muscle activity, myosin heavy chain transition, and hypertrophy (2013)
  • Author(s): Ohnuki Y, Umeki D, Cai W, Kawai N, Mototani Y, Shiozawa K, Jin HL, Fujita T, Tanaka E, Saeki Y, Okumura S
  • Journal Title: J Pharmacol Sci Volume: 123 Pages: 36-46
  • Peer Reviewed
• [Journal Article] Effects of chronic Akt/mTOR inhibition by rapamycin on mechanical overload-induced hypertrophy and myosin heavy chain transition in masseter muscle (2013)
  • Author(s): Umeki D, Ohnuki Y, Mototani Y, Shiozawa K, Fujita T, Nakamura Y, Saeki Y, Okumura S
  • Journal Title: J Pharmacol Sci Volume: 122 Pages: 278-288
  • NAID: 10031196201
  • Peer Reviewed
• [Journal Article] Effects of protein kinase A on the phosphorylation status and transverse stiffness of cardiac myofibrils (2013)
  • Author(s): Ohnuki Y, Okumura S et al.
  • Journal Title: J Pharmacol Sci Volume: 123 Pages: 279-283
  • NAID: 130003382605
  • Peer Reviewed
• [Journal Article] Role of masseter muscle beta2-adrenergic signaling in regulation of muscle activity, myosin heavy chain transition, and hypertrophy (2013)
  • Author(s): Ohnuki Y, Okumura S et al
  • Journal Title: J Pharamacol Sci Volume: 123 Pages: 36-46
  • Peer Reviewed
• [Journal Article] Effects of chronic Akt/mTOR inhibition by rapamycin on mechanical overload-induced hypertrophy and myosin heavy chain transition in masseter muscle (2013)
  • Author(s): Umeki D, Okumura S et al
  • Journal Title: J Pharamacol Sci Volume: 122 Pages: 278-288
  • NAID: 10031196201
  • Peer Reviewed
• [Journal Article] 歯学部における生理学教育について (2013)
  • Author(s): 奥村敏
  • Journal Title: 日本生理学会雑誌 Volume: 75 Pages: 229-230
• [Journal Article] Pharmacological stimulation of type 5 adenylyl cyclase stabilizes heart rate under both microgravity and hypergravity induced by parabolic flight (2012)
  • Author(s): Bai Y, Tsunematsu T, Jiao Q, Ohnuki Y, Mototani Y, Shiozawa K, Jin M, Cai W, Jin HL, Fujita T, Ichikawa Y, Suita K, Kurotani R, Yokoyama U, Sato M, Iwatsubo K, Ishikawa Y, Okumura S
  • Journal Title: J Pharmacol Sci Volume: 119 Pages: 381-389
  • NAID: 10031071685
  • Peer Reviewed
• [Journal Article] Inhibition of EP4 signaling attenuate aortic aneurysm formation (2012)
  • Author(s): Yokoyama U, Ishiwata R, Jin MH, Kato Y, Suzuki O, Jin H, Ichikawa Y, Kumagaya S, Katayama Y, Fujita T, Okumura S, Sato M, Sugimoto Y, Aoki H, Suzuki S, Masuda M, Minamisawa S, Ishikawa Y
  • Journal Title: Plos One Volume: 7
  • Peer Reviewed
• [Journal Article] Inhibition of phosphodiesterase type 3 dilates the rat ductus arteriosus without inducing intimal thickening (2012)
  • Author(s): Ichikawa Y, Yokoyama U, Iwamoto M, Oshikawa J, Okumura S, Sato M, Yokota S, Masuda M, Asou T, Ishikawa Y
  • Journal Title: Circ J Volume: 76 Pages: 2456-2464
  • NAID: 10030875150
  • Peer Reviewed
• [Journal Article] Effects of ascorbic acid on reactive oxygen species production in chemotherapy and hyperthermia inprostate cancer cell (2012)
  • Author(s): Fukumura H, Sato M, Kezuka K, Sato I, Feng X, Okumura S, Fujita T, Yokoyama U, Eguchi H, Ishikawa Y, Saito T
  • Journal Title: J Physiol Sci Volume: 62 Pages: 251-257
  • Peer Reviewed
• [Journal Article] (2012)
  • Author(s): Iwatsubo K, Brav C, Uechi M, Baljinnyam E, Nakamura T, Umemura M, Lai L, gao S, Yan L, Zhao X, Park M, Qiu H, Okumura S, Iwatsubo M, Vatner DE, Vatner SF, Ishikawa Y
  • Journal Title: Am J Physiol Heart Circ Physiol Volume: 302
  • Peer Reviewed
• [Journal Article] Pharmacological Stimulation of Type 5 Adenylyl Cyclase Stabilizes Heart Rate Under Both Microgravity and Hypergravity Induced by Parabolic Flight (2012)
  • Author(s): Bai Y, et al.
  • Journal Title: Journal of Pharmacological Sciences Volume: 119 Issue: 4 Pages: 381-389
  • DOI: 10.1254/jphs.12102FP
  • NAID: 10031071685
  • ISSN: 1347-8613, 1347-8648
  • Peer Reviewed
• [Journal Article] Inhibition of EP4 signaling attelluates aortic aneurysm formation (2012)
  • Author(s): Yokoyama U
  • Journal Title: PLoS One Volume: 7 Issue: 5 Pages: e36724-e36724
  • DOI: 10.1371/journal.pone.0036724
  • Peer Reviewed
• [Journal Article] Effect of ascorbic acid on reactive oxygen species production in chemotherapy and hyperthermia in prostate cancer cells. (2012)
  • Author(s): Fukumura H, et al.
  • Journal Title: J. Physiol. Sci. Volume: 62 Issue: 3 Pages: 251-257
  • DOI: 10.1007/s12576-012-0204-0
  • Peer Reviewed
• [Journal Article] Prevention of heart failure in mice by an antiviral agent that inhibits type 5 cardiac adenylyl cyclase. (2012)
  • Author(s): Iwatsubo K, Bravo C, Uechi M, Baljinnyam E, Nakamura T, Umemura M, Lai L, Gao S, Yan L, Park M, Qiu H, Okumura S, Iwatwsubo M, Vatner DE, Vatner SF, and Ishikawa Y.
  • Journal Title: Am J Physiol Heart Circ Physiol. Volume: 302 Issue: 12 Pages: H2622-H2628
  • DOI: 10.1152/ajpheart.00190.2012
  • Peer Reviewed
• [Journal Article] Secretoglobin 3A2 supresses bleomycin-induced pulmonary fibrosis by transforming growth factorβsignaling down-regulation (2011)
  • Author(s): Kurotani R, Okumura S, Matsubara T, Yokoyama U, Buckley JR, Tomita T, Kezuka K, Nagano T, Esposito D, Taylor TE, Gillette WK, Ishikawa Y, Abe H, Ward JM, Kimura S
  • Journal Title: J Biol Chem Volume: 286 Pages: 19682-19692
  • Peer Reviewed
• [Journal Article] Identification of transforming factor E3 (TFE3) as a receptor-independent activator of Gα16 (2011)
  • Author(s): Sato M, Hiraoka M, Suzuki H, Bai Y, Kurotani R, Yokoyama U, Okumura S, Cismowski MJ, Lanier SM, Ishikawa Y
  • Journal Title: J Biol Chem Volume: 286 Pages: 17766-17776
  • Peer Reviewed
• [Journal Article] The role of cytochrome p450 in ischemic heart disease (2011)
  • Author(s): Sato M, Yokoyama U, Fujita T, Okumura S, Ishikawa Y
  • Journal Title: Curr Drug Metab Volume: 12 Pages: 526-532
  • Peer Reviewed
• [Journal Article] Secretoglobin 3A2 suppresses bleomycin-induced pulmonary fibrosis by TGFbeta signaling down-regulation. (2011)
  • Author(s): Kurotani R, et al
  • Journal Title: J. Biol. Chem. Volume: 286 Issue: 22 Pages: 19682-19692
  • DOI: 10.1074/jbc.m111.239046
  • Peer Reviewed
• [Journal Article] The roles of cytochrome P450 in ischemic heart disease (2011)
  • Author(s): Sato M, Yokoyama U, Fujita T, Okumura S, Ishikawa Y
  • Journal Title: Current Drug Metabolism Volume: 12 Pages: 526-532
  • Peer Reviewed
• [Journal Article] Identification of transcription factor E3 (TFE3) as areceptor-independent activator of G α 16: Gene regulation by nuclear Ga subunit and it s activator. (2011)
  • Author(s): Sato M, et al
  • Journal Title: J Biol Chem. Volume: 286 Issue: 20 Pages: 17766-17776
  • DOI: 10.1074/jbc.m111.219816
  • Peer Reviewed
• [Presentation] Vidarabine, a selective cardiac adenylyl cyclase inhibitor, prevents ventricular arrhythmia in Calsequestrin 2 knockout mouse (2014)
  • Author(s): Suita K, Okumur a S, et al.
  • Organizer: 第91回日本生理学会大会
  • Place of Presentation: 鹿児島大学
• [Presentation] Roles of Epac in masseter muscle hypertrophy induced by chronic stimulation of beta 2 adorenoreceptor (2014)
  • Author(s): Ohnuki Y, Okumura S, et al.
  • Organizer: 第91回日本生理学会大会
  • Place of Presentation: 鹿児島大学
• [Presentation] Vidarabine, a selective cardiac adenylyl cyclase inhibitor, prevents ventricular arrhythmia in Calsequestrin 2 knockout mouse (2014)
  • Author(s): Suita K, Okumur a S, et al.
  • Organizer: 第78回日本循環器学会学術集会
  • Place of Presentation: 東京国際フォーラム
• [Presentation] Roles of Epac in masseter muscle hypertrophy induced by chronic stimulation of beta2-adrenoreceptor (2014)
  • Author(s): Ohnuki Y, Okumura S et al.
  • Organizer: The 91 Annual Meeting of the Physiological Societyof Japan
  • Place of Presentation: Kagoshima University
• [Presentation] Vidarabine, a selective cardiac adenylyl cyclase inhibitor, prevents ventricular arrhythmias in Calsequestrin 2 knockput mice (2014)
  • Author(s): Suita K, Okumura S et al.
  • Organizer: The 91 Annual Meeting of the Physiological Societyof Japan
  • Place of Presentation: Kagoshima University
• [Presentation] Vidarabine, a selective cardiac adenylyl cyclase inhibitor, prevents ventricular arrhythmias in Calsequestrin 2 knockput mice (2014)
  • Author(s): Suita K, Okumura S et al.
  • Organizer: The 78 th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: Tokyo International Forum
• [Presentation] Effects of beta2-adrenoceptor agonists on function and phenotype of rat masseter muscle (2013)
  • Author(s): Onuki Y, Okumura S
  • Organizer: The 55th Annual Meeting of Japanese Association for Oral Biology
  • Place of Presentation: Okayama University
• [Presentation] Relationship between natural bite size and body mass index (BMI) (2013)
  • Author(s): Shiozawa K, Okumura S
  • Organizer: The 55th Annual Meeting of Japanese Association for Oral Biology
  • Place of Presentation: Okayama Universuty
• [Presentation] George E Brown Memor ial Lecture and Molecular Mechanism of Hear t Failure (2012)
  • Author(s): Okumur a S, et al
  • Organizer: Disruption of Epac1 decreases phosphorylation of phospholamban and protects the heart against stress Amer ican Hear t Association Scientifc Scission 2012
  • Place of Presentation: Los Angeles in USA(Oral presentation)
• [Presentation] Epac activation protects heart from interleukin-6-induced cardiac dysfunction by inhibiting STAT/iNOS signaling (2011)
  • Author(s): Okumur a S,, et al.
  • Organizer: American Heart Association Scientific Sessions 2011
  • Place of Presentation: Orlando in USA(Oral presentation)
• [Presentation] Disruption of Epac1 protects heart from catecholamine-mediated cardiac fibrosis (2011)
  • Author(s): Okumura S, et al.
  • Organizer: 第75回日本循環器学会学術集会
  • Place of Presentation: 東京国際フォーラム
• [Presentation] Epac activation protects heart from interleukin-6-induced cardiac dysfunction by inhibiting STAT/iNOS signaling (2011)
  • Author(s): Satoshi Okumura, Meihua Jin, Fumika Kawamata, Hui-Ling Jin, Wenqian Cai, Yunzhe Bai, Kenji Suita, Yuko Hidaka, Takashi Tsunematsu, Yoshihiro Ishikawa
  • Organizer: American Heart Association Scientific Sessions 2011
  • Place of Presentation: Orange County Convention Center, Orlando, Florida, USA
• [Presentation] Disruption of Epac1 Protects Heart from Catecholamine-mediated Cardiac Fibrosis (2011)
  • Author(s): Okumura S, Cai W, Jin M, Bai Y, Tsunematsu T, HidakaY, Kurotani R, Ishikawa Y
  • Organizer: 第75回日本循環器学会学術集会
  • Place of Presentation: パシフィコ横浜、神奈川県横浜市
• [Presentation] Effects of beta-2 adrenoceptor agonists on function and phenotype of rat masseter muscle
  • Author(s): Ohnuki Y, Okumura S, et al.
  • Organizer: 第51回歯科基礎医学会総会
  • Place of Presentation: 岡山大学
• [Presentation] Disruption of Epac1 decreases phosphorylation of phospholamban and protects the heart against stress
  • Author(s): Satoshi Okumura et al
  • Organizer: American Heart Association Scientific Scission 2012
  • Place of Presentation: Los Angeles Convention Center (Los Angeles, CA, USA)
• [Presentation] Roles of Epac in muscle hypertrophy and fiber-type transition induced by beta2-adrenoceptor agonist in masseter muscle
  • Author(s): Yoshiki Ohnuki, Satoshi Okumura et al
  • Organizer: The 90 th Annual Meeting of the Physiological Society of Japan
  • Place of Presentation: TOWER HALL FUNABORI (Tokyo.Japan)
• [Presentation] Pharamacological inhibition of STAT3 protects heart from lipopolysaccharide-induced cardiac dysfunction through the inhibition of Jak2/STAT3/iNOS signaling
  • Author(s): Huiling Jin, Satoshi Okumura et al.
  • Organizer: The 90 th Annual Meeting of the Physiological Society of Japan
  • Place of Presentation: TOWER HALL FUNABORI (Tokyo.Japan)
• [Presentation] Vidarabine, an anti-herpesvirus agent, prevents atrial fibrillation in mice
  • Author(s): Kenji Suita, Satoshi Okumura et al.
  • Organizer: The 90 th Annual Meeting of the Physiological Society of Japan
  • Place of Presentation: TOWER HALL FUNABORI (Tokyo.Japan)
• [Presentation] Epac1 pathway plays an important role for thedevelopment of heart failure through the activation of PKA
  • Author(s): Cai Weniqian, Satoshi Okumura et al.
  • Organizer: The 90 th Annual Meeting of the Physiological Society of Japan
  • Place of Presentation: TOWER HALL FUNABORI (Tokyo.Japan)
• [Presentation] Relationship between masticatory perforformance and nasticatory behavior in humans
  • Author(s): Kouichi Shiozawa, Satoshi Okumura
  • Organizer: The 90 th Annual Meeting of the Physiological Society of Japan
  • Place of Presentation: TOWER HALL FUNABORI (Tokyo.Japan)
• [Presentation] 新規サイクリックAMP活性化因子Epacの咬筋肥大における役割
  • Author(s): 大貫芳樹、奥村敏
  • Organizer: 第54回歯科基礎医学会学術大会・総会
  • Place of Presentation: 奥羽大学（福島）
• [Presentation] 咀嚼能率と一口量との関係
  • Author(s): 塩澤光一、奥村敏
  • Organizer: 第54回歯科基礎医学会学術大会・総会
  • Place of Presentation: 奥羽大学（福島）
• [Book] 歯科基礎生理学第6版(共著) (2014)
• [Book] 基礎歯科生理学 (2014)
  • Author(s): 奥村敏 共著
  • Total Pages: 436
  • Publisher: 医歯薬出版
• [Remarks] 鶴見大学 歯学部 生理学講座
  • URL: http://dent.tsurumi-u.ac.jp/guide/course/basic/331
• [Remarks] 横浜市立大学 医学部 循環制御医学
  • URL: http://www-user.yokohama-cu.ac.jp/~seiri1/
• [Remarks] 愛知医科大学 医学部 生理学
  • URL: http://www.aichi-med-u.ac.jp/physio2/
• [Remarks] 鶴見大学歯学部生理学講座
  • URL: http://dent.tsurumi-u.ac.jp/guide/course/basic/331
• [Remarks] 鶴見大学歯学部生理学
  • URL: http://dent.tsurumi-u.ac.jp/guide/course/basic/331
• [Remarks] 横浜市立大学大学院医学研究科 循環制御医学
  • URL: http://www-user.yokohama-cu.ac.jp/~seiri1/
• [Remarks] 横浜市立大学 循環制御医学ホームページ
  • URL: http://www-user.yokohama-cu.ac.jp/~seiri1/index.html
• [Remarks] 鶴見大学 生理学ホームページ
  • URL: http://dent.tsurumi-u.ac.jp/guide/course/basic/331
• [Patent(Industrial Property Rights)] ビダラビンによる心房細動治療 (2012)
  • Inventor(s): 石川義弘、奥村 敏、吹田憲治
  • Industrial Property Rights Holder: 横浜市立大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2012-08-01
• [Patent(Industrial Property Rights)] ビダラビンによる心房細動治療 (2012)
  • Inventor(s): 石川義弘、奥村敏、吹田憲治
  • Industrial Property Rights Holder: 石川義弘、奥村敏、吹田憲治
  • Industrial Property Rights Type: 特許
  • Filing Date: 2012-08-01
  • Overseas
• [Patent(Industrial Property Rights)] アデニル酸シクラーゼの活性調節剤 (2011)
  • Inventor(s): 石川義弘、奥村 敏、星野雄二郎、井上 誠一
  • Industrial Property Rights Holder: 横浜市立大学、横浜国立大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2011-10-20
• [Patent(Industrial Property Rights)] ビダラビンによる心房細動治療 (2011)
  • Inventor(s): 石川義弘、奥村 敏、吹田憲治
  • Industrial Property Rights Holder: 横浜市立大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2011-222421
  • Filing Date: 2011-10-07
• [Patent(Industrial Property Rights)] ビダラビンによる心房細動治療 (2011)
  • Inventor(s): 石川義弘、奥村 敏、吹田憲冶
  • Industrial Property Rights Holder: 石川義弘、奥村 敏、吹田憲冶
  • Industrial Property Number: 2011-222421
  • Filing Date: 2011
• [Patent(Industrial Property Rights)] アデニル酸シクラーゼの活性調節剤 (2011)
  • Inventor(s): 石川義弘、奥村 敏、星野雄二郎、井上誠一
  • Industrial Property Rights Holder: 石川義弘、奥村 敏、星野雄二郎、井上誠一
  • Filing Date: 2011
  • Overseas