Significance of reciprocal expression of myocardian and MRTF-A during the development of vascular disease

2013 Fiscal Year Final Research Report

• Project/Area Number: 24659386
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Circulatory organs internal medicine
• Research Institution: Kyoto University
• Principal Investigator: KUWAHARA Koichiro 京都大学, 医学(系)研究科(研究院), 講師 (30402887)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: 分子血管病態学 / 転写調節

Research Abstract

Expression of myocardin-related transcription factor (MRTF)-A, a Rho signaling-responsive co-activator of serum response factor (SRF), was found to be increased in injured arteries and to be involved in the increase in proliferation and migration capacity in undifferentiated, activated vascular smooth muscle cells. Moreover, the MRTF-A inhibitor CCG1423 significantly reduced neointima formation following vascular injury in mice. MRTF-A could thus be a novel therapeutic target for the treatment of vascular diseases.

Research Products

• [Journal Article] The Effects of Super-Flux (High Performance) Dialyzer on Plasma Glycosylated Pro-B-Type Natriuretic Peptide (proBNP) and Glycosylated N-Terminal proBNP in End-Stage Renal Disease Patients on Dialysis (2014)
  • Author(s): Nakagawa Y, Nishikimi T, Kuwahara K, Yasuno S, Kinoshita H, Kuwabara Y, Nakao K, Minami T, Yamada C, Ueshima K, Ikeda Y, Okamoto H, Horii K, Nagata K, Kangawa K, Minamino N, Nakao K.
  • Journal Title: PLoS One Volume: 9(3) Pages: e92314
• [Journal Article] Identification of Chemicals Inducing Cardiomyocyte Proliferation in Developmental Stage-Specific Manner with Pluripotent Stem Cells (2013)
  • Author(s): Uosaki H, Magadum A, Seo K, Fukushima H, Takeuchi A, Nakagawa Y, Moyes KW, Narazaki G, Kuwahara K, Laflamme M, Matsuoka S, Nakatsuji N, Nakao K, Kwon C, Kass DA, Engel FB, Yamashita JK.
  • Journal Title: Circ Cardiovasc Genet Volume: 6(6) Pages: 624-33
• [Journal Article] Role of NRSF/REST in the Regulation of Cardiac Gene Expression and Function (2013)
  • Author(s): Kuwahara K.
  • Journal Title: Circ J Volume: 77(11) Pages: 2682-6
• [Journal Article] Angiotensin II Type 1a receptor signaling directly contributes to the increased arrhythmogenicity in cardiac hypertrophy (2013)
  • Author(s): Yasuno S, Kuwahara K, Kinoshita H, Yamada C, Nakagawa Y, Usami S, Kuwabara Y, Ueshima K, Harada M, Nishikimi T, Nakao K.
  • Journal Title: Br J Pharmacol Volume: 170(7) Pages: 1384-95
• [Journal Article] Adrenomedullin in Cardiovascular Disease : A Useful Biomarker, Its Pathological Roles and Therapeutic Application (2013)
  • Author(s): Nishikimi T, Kuwahara K, Nakagawa Y, Kangawa K, Nakao K.
  • Journal Title: Curr Protein Pept Sci Volume: 14(4) Pages: 256-267
• [Journal Article] Increased Expression of HCN Channels in the Ventricular Myocardium Contributes to Enhanced Arrhythmicity in Mouse Failing Hearts (2013)
  • Author(s): Kuwabara Y, Kuwahara K, Takano M, Kinoshita H, Arai Y, Yasuno S, Nakagawa Y, Igata S, Usami S, Minami T, Yamada Y, Nakao K, Yamada C, Shibata J, Nishikimi T, Ueshima K, Nakao K.
  • Journal Title: J Am Heart Assoc Volume: 2(3) Pages: e000150
• [Journal Article] Cardiac nuclear High Mobility Group Box 1 prevents the development of cardiac hypertrophy and heart failure (2013)
  • Author(s): Funayama A, Shishido T, Netsu S, Narumi T, Kadowaki S, Takahashi H, Miyamoto T, Watanabe T, Woo CH, Abe JI, Kuwahara K, Nakao K, Takeishi Y, Kubota I.
  • Journal Title: Cardiovasc Res Volume: 99(4) Pages: 657-64
• [Journal Article] Direct Immunochemiluminescent Assay for proBNP and Total BNP in Human Plasma proBNP and Total BNP Levels in Normal and Heart Failure (2013)
  • Author(s): Nishikimi T, Okamoto H, Nakamura M, Ogawa N, Horii K, Nagata K, Nakagawa Y, Kinoshita H, Yamada C, Nakao K, Minami T, Kuwabara Y, Kuwahara K, Masuda I, Kangawa K, Minamino N, Nakao K.
  • Journal Title: PLoS One Volume: 8(1) Pages: e53233
• [Journal Article] Angiotensin II-induced cardiac hypertrophy and fibrosis are promoted in mice lacking Fgf16 (2013)
  • Author(s): Matsumoto E, Sasaki S, Kinoshita H, Kito T, Ohta H, Konishi M, Kuwahara K, Nakao K, Itoh N.
  • Journal Title: Genes Cells Volume: 18(7) Pages: 544-553
• [Journal Article] Voltage-dependent N-type Ca2+ channels in endothelial cells contribute to oxidative stress-related endothelial dysfunction induced by angiotensin II in mice (2013)
  • Author(s): Nishida M, Ishikawa T, Saiki S, Sunggip C, Aritomi S, Harada E, Kuwahara K, Hirano K, Mori Y, Kim-Mitsuyama S.
  • Journal Title: Biochem Biophys Res Commun Volume: 434(2) Pages: 210-6
• [Journal Article] Determination of the B-type Natriuretic Peptide Level as a Criterion for Abnormalities in Japanese Individuals in Routine Clinical Practice : The J-ABS Multi-center Study (Japan Abnormal BNP Standard) (2013)
  • Author(s): Kawai M, Yoshimura M, Harada M, Mizuno Y, Hiramitsu S, Shimizu M, Shoda T, Kuwahara K, Miyagishima K, Ueshima K, Nakao K.
  • Journal Title: Intern Med Volume: 52(2) Pages: 171-7
• [Journal Article] [109th Scientific Meeting of the Japanese Society of Internal Medicine : symposium : 2. Translational research and evidence-based medicine (EBM) in internal medicine in Japan, translational research; 4) Translational research of endocrinology and metabolism] (2012)
  • Author(s): Hosoda K, Yasoda A, Ebihara K, Kuwahara K, Mukouyama M, Nakao K.
  • Journal Title: Nihon Naika Gakkai Zasshi Volume: 101(9) Pages: 2552-62
• [Journal Article] Complexity of molecular forms of B-type natriuretic peptide in heart failure (2012)
  • Author(s): Nishikimi T, Kuwahara K, Nakagawa Y, Kangawa K, Minamino N, Nakao K.
  • Journal Title: Heart Volume: 99(10) Pages: 677-679
• [Journal Article] Reciprocal expression of MRTF-A and myocardin is crucial for pathological vascular remodeling in mice (2012)
  • Author(s): Minami T, Kuwahara K, Nakagawa Y, Takaoka M, Kinoshita H, Nakao K, Kuwabara Y, Yamada Y, Yamada C, Shibata J, Usami S, Yasuno S, Nishikimi T, Ueshima K, Sata M, Nakano H, Seno T, Kawahito Y, Sobue K, Kimura A, Nagai R and Nakao K.
  • Journal Title: EMBO J Volume: 31(23) Pages: 4428-40
• [Journal Article] In vivo site-specific transfection of naked plasmid DNA in mice using a tissue suction device (2012)
  • Author(s): Shimizu K, Kawakami S, Hayashi K, Kinoshita H, Kuwahara K, Nakao K, Hashida M, Konishi S.
  • Journal Title: Plos One Volume: 7(7) Pages: e41319
• [Presentation] 維持血液透析患者におけるproBNPについての検討 (2013)
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  • Organizer: 第17回日本心不全学会学術集会
  • Place of Presentation: 大宮ソニックシティ(埼玉)
  • Year and Date: 20131128-30
• [Presentation] ナトリウム利尿ペプチド発現制御機構解明による心血管病治療標的の同定 (2013)
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  • Place of Presentation: 千里、大阪
  • Year and Date: 20131122-23
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  • Organizer: 第17回日本心血管内分泌代謝学会総会
  • Place of Presentation: 千里、大阪
  • Year and Date: 20131122-23
• [Presentation] 透析中の末期腎不全患者における血中proBNPについての検討 (2013)
  • Author(s): 中川靖章、錦見俊雄、桑原宏一郎、保野慎治、木下秀之、桒原佳宏、中尾一泰、山田千夏、上嶋健治、南野直人、中尾一和
  • Organizer: 第36回日本高血圧学会
  • Place of Presentation: 大阪
  • Year and Date: 20131024-26
• [Presentation] Impact of C-type Natriuretic Peptide Derived from Vascular Endothelial Cells on Blood Pressure (2013)
  • Author(s): Kazuhiro Nakao, Koichiro Kuwahara, Toshio Nishikimi, Yasuaki Nakagawa, Satoru Usami, Hideyuki Kinoshita, Takeya Minami, Yoshihiro Kuwabara, Chinatsu Yamada, Yuko Yamada, Takeshi Tokudome, Yoko M. Nakao, Shinji Yasuno, Kenji Kangawa
  • Organizer: 第36回日本高血圧学会
  • Place of Presentation: 大阪
  • Year and Date: 20131024-26
• [Presentation] TRPC3/6阻害による肺動脈性肺高血圧症抑制効果の検討 (2013)
  • Author(s): 木下秀之、桑原宏一郎、清中茂樹、森泰生、赤城達、中村一文、山田千夏、桒原佳宏、中川靖章、中尾一和
  • Organizer: 第1回日本肺高血圧学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 20131013-14
• [Presentation] 透析患者における血中B型(脳性)ナトリウム利尿ペプチド前駆体proBNPについての検討 (2013)
  • Author(s): 中川靖章、錦見俊雄、桑原宏一郎、保野慎治、木下秀之、桒原佳宏、中尾一泰、山田千夏、上嶋健治、中尾一和
  • Organizer: 第61回心臓病学会
  • Place of Presentation: ホテル日航熊本、鶴やホール(熊本)
  • Year and Date: 20130920-22
• [Presentation] Myocardin-related transcription factor-A plays a pivotal role in vascular remodeling (2013)
  • Author(s): Koichiro Kuwahara, Kazuwa Nakao
  • Organizer: 第45回日本動脈硬化学会
  • Place of Presentation: 東京
  • Year and Date: 20130718-19
• [Presentation] Effect of O-linked Glycosylation of plasma N-terminal proBNP on NT-proBNP assay in hemodyalysis patients (2013)
  • Author(s): 中川靖章、錦見俊雄、桑原宏一郎、保野慎治、木下秀之、桒原佳宏、中尾一泰、山田千夏、上嶋健治、中尾一和
  • Organizer: 心筋代謝研究会
  • Place of Presentation: キャノンマーケティングジャパン株式会社3階ホール(東京)
  • Year and Date: 20130713-14
• [Presentation] 肺動脈性肺高血圧症に対する新規治療標的としてのTRPC3/6阻害効果の検討 (2013)
  • Author(s): 木下秀之、桑原宏一郎、清中茂樹、森泰生、赤木達、中村一文、桒原佳宏、中川靖章、錦見俊雄、中尾一和
  • Organizer: 第2回日本肺循環学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 20130622-23
• [Presentation] 透析患者における血中N端proBNPの糖鎖修飾と測定系への影響について (2013)
  • Author(s): 中川靖章、錦見俊雄、桑原宏一郎、保野慎治、木下秀之、桒原佳宏、中尾一泰、山田千夏、上嶋健治、中尾一和
  • Organizer: 第2回臨床高血圧フォーラム
  • Place of Presentation: JPタワーホール&カンファレンス(東京)
  • Year and Date: 20130525-26
• [Presentation] 左室リモデリング進行及び催不整脈性抑制におけるレニンーアンジオテンシン系の検討 (2013)
  • Author(s): 山田千夏、桑原宏一郎、木下秀之、錦見俊雄、中尾一泰、桒原佳宏、保野慎治、中川靖章、上嶋健治、中尾一和
  • Organizer: 第86回日本内分泌学会学術総会
  • Place of Presentation: 仙台
  • Year and Date: 20130425-27
• [Presentation] 血管壁ナトリウム利尿ペプチド系の意義の解明-血管内皮細胞特異的C型ナトリウム利尿ペプチド( C N P )ノックアウトマウスの解析- (2013)
  • Author(s): 中尾一泰桑原宏一郎錦見俊雄中川靖章木下秀之宇佐美覚桑原佳宏南丈也山田千夏山田優子保野慎治上嶋健治曽根正勝寒川賢治中尾一和
  • Organizer: 第50回臨床分子医学会
  • Place of Presentation: 東京
  • Year and Date: 20130412-13
• [Presentation] 拡張型心筋症モデルマウスにおける左室リモデリング及び不整脈源性基質形成におけるレニン―アンジオテンシン系の意義 (2013)
  • Author(s): 山田千夏,桑原宏一郎,木下秀之,錦見俊雄,中尾一泰,桒原佳宏,中川靖章,中尾一和
  • Organizer: 第50回臨床分子医学会
  • Place of Presentation: 東京
  • Year and Date: 20130412-13
• [Presentation] 心不全・突然死モデルマウスを用いた心不全の病態解明と新規治療標的の同定 (2013)
  • Author(s): 桑原宏一郎、中尾一和
  • Organizer: 第90回日本生理学会大会
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  • Year and Date: 20130327-29
• [Presentation] Elucidation of molecular mechanisms underlying the regulation and action of cardiovascular hormones to find novel therapeutic targets for cardiovascular diseases (2013)
  • Author(s): Koichiro Kuwahara
  • Organizer: The77th Annual Scientific Meeting of The Japanese CirculationSociety
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  • Year and Date: 20130315-17
• [Presentation] Multi-organ communication in sudden arrhythmic death accompanied with heart failure (2013)
  • Author(s): Koichiro Kuwahara, Kazuwa Nakao
  • Organizer: The77th Annual Scientific Meeting of The Japanese CirculationSociety
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  • Year and Date: 20130315-17
• [Presentation] Contribution of renin-angiotensin system to the generation of arrhythmogenic substrate in mice with dilated cardiomyopathy and lethal arrhythmia (2013)
  • Author(s): Chinatsu Yamada, Koichiro Kuwahara, et al.
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  • Place of Presentation: San Diego
  • Year and Date: 2013-06-29
• [Presentation] 左室リモデリング進行及び催不整脈性抑制におけるレニン阻害の有用性の検討 (2012)
  • Author(s): 山田千夏桑原宏一郎木下秀之錦見俊雄桑原佳宏南丈也中尾一泰中川靖章中尾一和
  • Organizer: 第15回日本心血管内分泌代謝学会学術総会
  • Place of Presentation: 東京都
  • Year and Date: 20121125-26
• [Presentation] N-Type Ca2+ Channel Blockade Prevents Sudden Death in Mice with Heart Failure (2012)
  • Author(s): Yuko Yamada, Koichiro Kuwahara, Hideyuki Kinoshita, Yoshihiro Kuwabara, Yasuaki Nakagawa, Chinatsu Yamada, Takeya Minami, Shinji Yasuno, Kazuhiro Nakao, Toshio Nishikimi, Kenji Ueshima, Yasuo Mori, Wataru Shimizu, Kenji Kangawa, Kazuwa Nakao
  • Organizer: 第29回国際心臓研究学会(ISHR)日本部会
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  • Year and Date: 20121026-27
• [Presentation] Reciprocal expression of MRTF-A and Myocardin is crucial for pathological vascular remodeling in mice (2012)
  • Author(s): Takeya Minami, Koichiro Kuwahara, Yasuaki Nakagawa, Hideyuki Kinoshita, Kazuhiro Nakao, Yoshihiro Kuwabara, Toshio Nishikimi, Kazuwa Nakao
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  • Year and Date: 20121026-27
• [Book] ガイドライン外来診療2014 (2014)
  • Author(s): 桑原宏一郎、木村剛
  • Total Pages: 455-460
  • Publisher: 日経メディカル開発
• [Book] 変貌する心不全診療 (2013)
  • Author(s): 中川靖章、桑原宏一郎
  • Publisher: 南江堂
• [Remarks]
  • URL: http://www.kuhp.kyoto-u.ac.jp/~med2/jpn/research/cardio.html