2017 Fiscal Year Annual Research Report
Development of new early diagnosis, prevention and treatment of cardiovascular disease by clinical application of basic research
Project/Area Number |
15H04816
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Research Institution | Tohoku University |
Principal Investigator |
佐藤 公雄 東北大学, 高度教養教育・学生支援機構, 准教授 (80436120)
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Co-Investigator(Kenkyū-buntansha) |
宮田 敏 東北大学, 医学系研究科, 准教授 (60360343)
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Project Period (FY) |
2015-04-01 – 2018-03-31
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Keywords | 循環器・高血圧 / 肺高血圧症 / バイオマーカー / 創薬 / 基礎研究の臨床応用 / ハイスループットスクリーニング |
Outline of Annual Research Achievements |
【目的】 心血管病発症における酸化ストレス分泌蛋白サイクロフィリンA (CyPA)およびその受容体Basiginの基礎研究成果を基盤とし、臨床応用研究を加速させ、迅速診断薬開発や治療薬スクリーニング(創薬)を行う。
【結果】 各種の遺伝子改変動物を用いた基礎研究を継続し、CyPAが肺高血圧症にとって重要蛋白であることを確認し、論文発表を行った。さらに、分泌蛋白としての特徴に着目し、ヒト肺高血圧症患者の末梢血での血漿中CyPA濃度の測定法を開発し、患者群で健常者群に比較して、濃度が上昇していることを確認した。さらに、CyPA高濃度群と低濃度群に分け、長期的な予後調査を行ったところ、血漿中CyPA濃度が高い群で、明らかに生命予後が不良であった。さらに、患者由来の組織や血液検体およびハイスループット・スクリーニング(HTS)システムを用い、CyPA分泌抑制・細胞外CyPA受容体阻害に着目した治療薬のスクリーニングを進めた。スクリーニングは終了し、肺高血圧モデルマウスにおける有効性の検証を進めた。
【学会・論文報告】 国内外の学会やシンポジウムで報告し(日本循環器学会総会シンポジウム、米国心臓病学会議、欧州心臓学会議)、12編の論文発表および5件の特許出願を行った。さらに、4542の既存薬ライブラリーからのハイスループットスクリーニングにより、有効な低分子化合物が数種類まで絞り込まれ、新しい治療薬としての可能性につきモデル動物での検証を進めた。
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Research Progress Status |
29年度が最終年度であるため、記入しない。
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Strategy for Future Research Activity |
29年度が最終年度であるため、記入しない。
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[Journal Article] Selenoprotein P promotes vascular smooth muscle cell proliferation and pulmonary hypertension -A possible novel therapeutic target-2018
Author(s)
Kikuchi N, Satoh K, Kurosawa R, Yaoita N, Md. Elias Al-Mamun, Mohammad Abdul Hai Siddique, Omura J, Satoh T, Nogi M, Sunamura S, Miyata S, Shimokawa H.
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Journal Title
Circulation
Volume: in press
Pages: in press
Peer Reviewed / Open Access
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[Journal Article] Sex differences in hemodynamic responses and long-term survival to optimal medical therapy in patients with pulmonary arterial hypertension.2018
Author(s)
Kozu K, Sugimura K, Aoki T, Tatebe S, Yamamoto S, Yaoita N, Shimizu T, Nochioka K, Sato H, Konno R, Satoh K, Miyata S, Shimokawa H.
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Journal Title
Heart Vessels.
Volume: in press
Pages: in press
DOI
Peer Reviewed / Open Access
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[Journal Article] European society of cardiology (ESC) annual congress report from Barcelona 2017.2017
Author(s)
Satoh K, Takahashi J, Matsumoto Y, Tatebe S, Aoki T, Kikuchi Y, Hao K, Ohyama K, Nogi M, Suda A, Kasahara S, Sato K, Ichijo S, Shimokawa H.
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Journal Title
Circ J.
Volume: 81
Pages: 1758-1763
DOI
Peer Reviewed / Open Access
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[Journal Article] Comprehensive evaluation of the effectiveness and safety of balloon pulmonary angioplasty for inoperable chronic thromboembolic pulmonary hypertension - Long-term effects and procedure-related complications -2017
Author(s)
Aoki T, Sugimura K, Tatebe S, Miura M, Yamamoto S, Yaoita N, Suzuki H, Sato H, Kozu K, Konno R, Miyata S, Nochioka K, Satoh K, Shimokawa H.
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Journal Title
Eur Heart J.
Volume: 38
Pages: 3152-3159
DOI
Peer Reviewed / Open Access
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[Journal Article] The efficacy of a genetic analysis of the BMPR2 gene in a patient with severe pulmonary arterial hypertension and an atrial septal defect treated with bilateral lung transplantation.2017
Author(s)
Tatebe S, Sugimura K, Aoki T, Yamamoto S, Yaoita N, Suzuki H, Sato H, Kozu K, Konno R, Satoh K, Fukuda K, Adachi O, Saito R, Nakanishi N, Morisaki H, Oyama K, Saiki Y, Okada Y, Shimokawa H.
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Journal Title
Intern Med.
Volume: 56
Pages: 3193-3197
DOI
Peer Reviewed / Open Access
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[Presentation] Selenoprotein P promotes the development of pulmonary arterial hypertension-A Possible Novel Therapeutic Target-2018
Author(s)
Kikuchi N, Satoh K, Kurosawa R, Yaoita N, Elias-Al-Mamun M, Abdul Hai Siddique M, Omura J, Satoh T, Nogi M, Sunamura S, Miyata S, Saito Y, Hoshikawa Y, Okada Y, Shimokawa H.
Organizer
World Symposium on Pulmonary Hypertension (2018年2月27~3月1日, Nice, France)
Int'l Joint Research
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[Presentation] ADAMTS8 Promotes the Development of pulmonary arterial hypertension and right ventricular failure-A possible novel therapeutic target-2018
Author(s)
Satoh K, Omura J, Kikuchi N, Satoh T, Kurosawa R, Nogi M, Sunamura S, Ohtsuki T, Elias-Al-Mamun M, Abdul Hai Siddique M, Yaoita N, Miyata S, Hoshikawa Y, Okada Y, Shimokawa H.
Organizer
World Symposium on Pulmonary Hypertension (2018年2月27~3月1日, Nice, France)
Int'l Joint Research
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[Presentation] Identification of celastramycin as a novel therapeutic agent for pulmonary arterial hypertension -High-throughput screening of 5,562 compounds-2018
Author(s)
Kurosawa R, Satoh K, Kikuchi N, Satoh T, Omura J, Nogi M, Sunamura S, Ohtsuki T, Yaoita N, Abdul Hai Siddique M, Elias-Al-Mamun M, Shimizu T, Shimokawa H.
Organizer
World Symposium on Pulmonary Hypertension (2018年2月27~3月1日, Nice, France)
Int'l Joint Research
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[Presentation] Different roles of myocardial ROCK1 and ROCK2 in response to chronic pressure-overload in mice.2018
Author(s)
Sunamura S, Satoh K, Shimizu T, Suzuki K, Ikeda S, Kudo S, Omura J, Kikuchi N, Satoh T, Kurosawa R, Nogi M, Ohtsuki T, Shimokawa H.
Organizer
World Symposium on Pulmonary Hypertension (2018年2月27~3月1日, Nice, France)
Int'l Joint Research
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[Presentation] Identification of Emetine as a Novel Therapeutic Agent for Pulmonary Hypertension in Rats -High-throughput Screening of 5,562 Compounds-2018
Author(s)
Abdul Hai Siddique M, Satoh K, Kurosawa R, Elias-Al-Mamun M, Kikuchi N, Omura J, Satoh T, Nogi M, Sunamura S, Shimokawa H.
Organizer
World Symposium on Pulmonary Hypertension (2018年2月27~3月1日, Nice, France)
Int'l Joint Research
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[Presentation] Prognostic Impacts of Soluble Form of Basigin in Patients with Chronic Heart Failure -From a Prospective Large Clinical Trial with 1,147 Patients-2018
Author(s)
Satoh K, Ohtsuki T, Miyata S, Miura M, Nochioka K, Sunamura S, Suzuki K, Nogi M, Kurosawa R, Omura J, Kikuchi N, Satoh T, Aoki T, Tatebe S, Sugimura K, Sakata Y, Shimokawa H.
Organizer
第82回日本循環器学会学術集会(3月23日~25日、2018年、大阪市)
Int'l Joint Research
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[Presentation] Rho-kinase and Cyclophilin A as Novel Therapeutic Targets for Cardiac Dysfunction and Post-Capillary Pulmonary Hypertension2018
Author(s)
Sunamura S, Satoh K, Kurosawa R, Ohtsuki T, Kikuchi N, Md Elias Al-Mamun, Shimizu T, Ikeda S, Suzuki K, Satoh T, Omura J, Nogi M, Mohammad Abdul Hai Siddique, Miyata S, Miura M, Shimokawa H.
Organizer
第82回日本循環器学会学術集会(3月23日~25日、2018年、大阪市)
Int'l Joint Research
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[Presentation] SmgGDS Prevents Thoracic Aortic Aneurysm Formation and Rupture by Phenotypic Preservation of Aortic Smooth Muscle Cells2018
Author(s)
Nogi M, Satoh K, Sunamura S, Kikuchi N, Sato T, Kurosawa R, Omura J, Md Elias Al-Mamun, Mohammad Abdul Hai Siddique, Kudo S, Akiyama M, Kawamoto S, Saiki Y, Shimokawa H.
Organizer
第82回日本循環器学会学術集会(3月23日~25日、2018年、大阪市)
Int'l Joint Research
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[Presentation] Normalization of Hemodynamic Responses to Exercise as a Final Goal of Balloon Pulmonary Angioplasty in Patients with CTEPH2018
Author(s)
Aoki T, Sugimura K, Tatebe S, Yamamoto S, Shimizu T, Yaoita N, Sato H, Kouzu K, Konno R, Terui Y, Nochioka K, Satoh K, Shimokawa H.
Organizer
第82回日本循環器学会学術集会(3月23日~25日、2018年、大阪市)
Int'l Joint Research
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[Presentation] Selenoprotein P Promotes Vascular Smooth Muscle Cell Proliferation and Pulmonary Hypertension -A Possible Novel Therapeutic Target-2018
Author(s)
Kikuchi N, Satoh K, Kurosawa R, Yaoita N, Md. Elias Al-Mamun, Mohammad Abdul Hai Siddique, Omura J, Sato T, Nogi M, Sunamura S, Miyata S, Shimokawa H.
Organizer
第82回日本循環器学会学術集会(3月23日~25日、2018年、大阪市)
Int'l Joint Research
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[Presentation] Sex Differences in Hemodynamic Responses and Long-term Survival to Optimal Medical Therapy in Patients with Pulmonary Arterial Hypertension2018
Author(s)
Kozu K, Sugimura K, Aoki T, Tatebe S, Yamamoto S, Yaoita N, Shimizu T, Nochioka K, Sato H, Konno R, Satoh K, Miyata S, Shimokawa H.
Organizer
第82回日本循環器学会学術集会(3月23日~25日、2018年、大阪市)
Int'l Joint Research
-
[Presentation] Identification of Emetine as a Novel Therapeutic Agent for Pulmonary Hypertension in Rats -High-throughput Screening of 5,562 Compounds-2018
Author(s)
Mohammad Abdul Hai Siddique, Satoh K, Kurosawa R, Md. Elias Al-Mamun, Kikuchi N, Omura J, Satoh T, Nogi M, Sunamura S, Shimokawa H.
Organizer
第82回日本循環器学会学術集会(3月23日~25日、2018年、大阪市)
Int'l Joint Research
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[Presentation] Important Prognostic Impacts of Serum Levels of Adipsin in Patients with Coronary Artery Disease2018
Author(s)
Ohtsuki T, Satoh K, Shimizu T, Ikeda S, Yaoita N, Sato T, Omura J, Kikuchi N, Kurosawa R, Sunamura S, Nogi M, Sugimura K, Aoki T, Tatebe S, Nochioka K, Yamamoto S, Takahashi J, Miyata S, Shimokawa H.
Organizer
第82回日本循環器学会学術集会(3月23日~25日、2018年、大阪市)
Int'l Joint Research
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[Presentation] Identification of Celastramycin as a Novel Therapeutic Agent for Pulmonary Arterial Hypertension -High-throughput Screening of 5,562 Compounds-2018
Author(s)
Kurosawa R, Satoh K, Kikuchi N, Omura J, Sato T, Nogi M, Sunamura S, Al-Mamun Md. Elias, Mohammad Abdul Hai Siddique, Shimokawa H.
Organizer
第82回日本循環器学会学術集会(3月23日~25日、2018年、大阪市)
Int'l Joint Research
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[Presentation] Clinical Profiles of Pregnant Women with Heart Disease2018
Author(s)
Tatebe S, Sugimura K, Saito M, Sakata Y, Satoh K, Aoki T, Yamamoto S, Shimizu T, Sato H, Otsuki T, Kozu K, Konno R, Terui Y, Kawano K, Kimura M, Adachi O, Saiki Y, Shimokawa H.
Organizer
第82回日本循環器学会学術集会(3月23日~25日、2018年、大阪市)
Int'l Joint Research
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[Presentation] Hepatitis C Virus Positivity Adversely Impacts Cardiac Functions and Long-term Prognosis in Patients with Adult Congenital Heart Disease2018
Author(s)
Konno R, Tatebe S, Sugimura K, Satoh K, Aoki T, Yamamoto S, Shimizu T, Sato H, Kozu K, Terui Y, Adachi O, Kimura M, Saiki Y, Shimokawa H.
Organizer
第82回日本循環器学会学術集会(3月23日~25日、2018年、大阪市)
Int'l Joint Research
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[Presentation] < Cournand and Comroe Young Investigator Award >Selenoprotein P promotes the development of pulmonary arterial hypertension-A Possible Novel Therapeutic Target-2017
Author(s)
Kikuchi N, Satoh K, Kurosawa R, Yaoita N, Elias-Al-Mamun M, Abdul Hai Siddique M, Omura J, Satoh T, Nogi M, Sunamura S, Miyata S, Saito Y, Hoshikawa Y, Okada Y, Shimokawa H.
Organizer
American Heart Association (AHA) Scientific Sessions (2017年11月11~15日, Anaheim, USA)
Int'l Joint Research
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[Presentation] Rivaroxaban prevents the development of chronic thromboembolic pulmonary hypertension in mice- Novel beneficial effects of the FXa inhibitor2017
Author(s)
Elias-Al-Mamun M, Satoh K, Satoh T, Yaoita N, Abdul Hai Siddique M, Kikuchi N, Omura J, Kurosawa R, Sunamura S, Nogi M, Ohtsuki T, Shimokawa H.
Organizer
American Heart Association (AHA) Scientific Sessions (2017年11月11~15日, Anaheim, USA)
Int'l Joint Research
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[Presentation] ADAMTS8 Promotes the Development of pulmonary arterial hypertension and right ventricular failure-A possible novel therapeutic target-2017
Author(s)
Omura J, Satoh K, Kikuchi N, Satoh T, Kurosawa R, Nogi M, Sunamura S, Ohtsuki T, Elias-Al-Mamun M, Abdul Hai Siddique M, Yaoita N, Miyata S, Hoshikawa Y, Okada Y, Shimokawa H.
Organizer
American Heart Association (AHA) Scientific Sessions (2017年11月11~15日, Anaheim, USA)
Int'l Joint Research
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[Presentation] Plasma cyclophilin A as a useful biomarker for evaluation of the effects of balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension.2017
Author(s)
Kozu K, Satoh K, Shimizu T, Aoki T, Tatebe S, Yamamoto S, Sato H, Ohtsuki T, Konno R, Miyata S, Sugimura K, Shimokawa H.
Organizer
American Heart Association (AHA) Scientific Sessions (2017年11月11~15日, Anaheim, USA)
Int'l Joint Research
-
[Presentation] Identification of celastramycin as a novel therapeutic agent for pulmonary arterial hypertension -High-throughput screening of 5,562 compounds-2017
Author(s)
Kurosawa R, Satoh K, Kikuchi N, Satoh T, Omura J, Nogi M, Sunamura S, Ohtsuki T, Yaoita N, Abdul Hai Siddique M, Elias-Al-Mamun M, Shimizu T, Shimokawa H.
Organizer
American Heart Association (AHA) Scientific Sessions (2017年11月11~15日, Anaheim, USA)
Int'l Joint Research
-
[Presentation] Different roles of myocardial ROCK1 and ROCK2 in response to chronic pressure-overload in mice.2017
Author(s)
Sunamura S, Satoh K, Shimizu T, Suzuki K, Ikeda S, Kudo S, Omura J, Kikuchi N, Satoh T, Kurosawa R, Nogi M, Ohtsuki T, Shimokawa H.
Organizer
American Heart Association (AHA) Scientific Sessions (2017年11月11~15日, Anaheim, USA)
Int'l Joint Research
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[Presentation] Prognostic impacts of plasma levels of cyclophilin A in patients with heart failure.2017
Author(s)
Ohtsuki T, Satoh K, Shimizu T, Ikeda S, Yaoita N, Satoh T, Omura J, Kikuchi N, Kurosawa R, Sunamura S, Nogi M, Sugimura K, Aoki T, Tatebe S, Miyata S, Shimokawa H.
Organizer
American Heart Association (AHA) Scientific Sessions (2017年11月11~15日, Anaheim, USA)
Int'l Joint Research
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[Presentation] Protective roles of small GTP-binding protein GDP dissociation stimulator against angiotensin II-induced thoracic aortic aneurysm formation and rupture in mice -A possible novel therapeutic target-2017
Author(s)
Nogi M, Satoh K, Kudo S, Satoh T, Omura J, Kikuchi N, Sunamura S, Kurosawa R, Ohtsuki T, Elias-Al-Mamun M, Abdul Hai Siddique M, Akiyama M, Shunsuke K, Saiki Y, Shimokawa H.
Organizer
American Heart Association (AHA) Scientific Sessions (2017年11月11~15日, Anaheim, USA)
Int'l Joint Research
-
[Presentation] Identification of Emetine as a Novel Therapeutic Agent for Pulmonary Hypertension in Rats -High-throughput Screening of 5,562 Compounds-2017
Author(s)
Abdul Hai Siddique M, Satoh K, Kurosawa R, Elias-Al-Mamun M, Kikuchi N, Omura J, Satoh T, Nogi M, Sunamura S, Shimokawa H.
Organizer
American Heart Association (AHA) Scientific Sessions (2017年11月11~15日, Anaheim, USA)
Int'l Joint Research
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[Presentation] <Young Investigator Awards Session: Basic Science>Thrombin activatable fibrinolysis inhibitor promotes development of chronic thromboembolic pulmonary hypertension -A possible novel therapeutic target-.2017
Author(s)
Satoh T, Satoh K, Yaoita N, Elias-Al-Mamun M, M.A.H. Siddique, Kikuchi N, Omura J, Kurosawa R, Sunamura S, Nogi M, Otsuki T, Miyata S, Shimokawa H.
Organizer
European Society Congress (ESC) Congress 2017 (2017年8月26~8月30日, Barcelona, Spain)
Int'l Joint Research
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[Presentation] <Best Posters Sessions> (Best Poster Award受賞)Balloon pulmonary angioplasty ameliorates long-term survival of patients with inoperable chronic thromboembolic pulmonary hypertension.2017
Author(s)
Tatebe S, Sugimura K, Aoki T, Yamamoto S, Yaoita N, Sato H, Konno R, Satoh K, Shimokawa H.
Organizer
European Society Congress (ESC) Congress 2017 (2017年8月26~8月30日, Barcelona, Spain)
Int'l Joint Research
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[Presentation] <Best Posters Sessions> Protective roles of small GTP-binding protein GDP dissociation stimulator against angiotensin II-induced thoracic aortic aneurysm formation and rupture in mice -A possible novel therapeutic target-.2017
Author(s)
Nogi M, Satoh K, Kudo S, Omura J, Kikuchi N, Satoh T, Sunamura S, Kurosawa R, Elias-Al-Mamun M, M.A.H. Siddique, Ohtsuki T, Shimokawa H.
Organizer
European Society Congress (ESC) Congress 2017 (2017年8月26~8月30日, Barcelona, Spain)
Int'l Joint Research
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[Presentation] <Interventions in the pulmonary circulation> (JCS-ESC Networking Event-Best Abstract Award受賞)Comprehensive evaluation of the effectiveness and safety of balloon pulmonary angioplasty for inoperable chronic thromboembolic pulmonary hypertension - long-term effects and complications.2017
Author(s)
Aoki T, Sugimura K, Tatebe S, Miura M, Yamamoto S, Yaoita N, Suzuki H, Sato H, Kozu K, Konno R, Nochioka K, Satoh K, Shimokawa H.
Organizer
European Society Congress (ESC) Congress 2017 (2017年8月26~8月30日, Barcelona, Spain)
Int'l Joint Research
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[Presentation] <Moderated Posters Sessions>Rivaroxaban prevents the development of chronic thromboembolic pulmonary hypertension in mice- Novel beneficial effects of the FXa inhibitor-.2017
Author(s)
Elias-Al-Mamun M, Satoh K, Satoh T, Yaoita N, M.A.H. Siddique, Kikuchi N, Omura J, Kurosawa R, Sunamura S, Nogi M, Ohtsuki T, Shimokawa H.
Organizer
European Society Congress (ESC) Congress 2017 (2017年8月26~8月30日, Barcelona, Spain)
Int'l Joint Research
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[Presentation] Protective Roles of Small GTP-binding Protein GDP Dissociation Stimulator Against Angiotensin II-induced Thoracic Aortic Aneurysm Formation and Rupture in Mice -A Possible Novel Therapeutic Target-2017
Author(s)
Nogi M, Satoh K, Kudo S, Omura J, Kikuchi N, Satoh T, Sunamura S, Kurosawa R, Ohtsuki T, Suzuki K, Shimokawa H.
Organizer
Scientific Session 2017 of the Arteriosclerosis, Thrombosis and Vascular Biology/ Perihperal Vascular Disease Council (May 4-6, 2017, Minneapolis, USA)
Int'l Joint Research
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