The signaling network between endothelium and myocardium responsible for myocardial protection

• Project/Area Number: 21590930
• 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: Osaka University
• Principal Investigator: NAKAOKA Yoshikazu 大阪大学, 大学院・医学系研究科, 助教 (90393214)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2011: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: angiopoietin-1 / 冠血管 / 冠静脈 / 心筋 / 内皮 / パラクラインシグナル / neuregulin-1 / EphB4 / 静動洞 / 静脈分化 / Neuregulin-1 / 心不全 / Tie2 / 心筋-内皮細胞間相互作用 / 心内膜内皮 / 心外膜 / ErbB

Research Abstract

To reveal the role of angiopoietin-1(Ang1) secreted from myocardium, we crossed Ang1flox mice withα-MHC-Cre transgenic mice to create cardiomyocyte-speicific Ang1 knockout(Ang1 CKO) mice. Ang1 CKO mice showed embryonic lethality between E12. 5 and 14. 5 with defects in(1) attachment between endocardial endothelium and ventricular traveculae,(2) development of both traveculae and compact layer, and(3) coronary vessel formation. We performed immunohistochemical analysis using CD31 antibody and found that Ang1 CKO mice exhibit the defects in coronary vein formation, namely' coronary venogenesis'.

Research Products

• [Journal Article] 冠動脈疾患研究の・治療の進歩と今後の課題 (2011)
  • Author(s): 中岡良和、小室一成
  • Journal Title: 日本臨床 Volume: 69(Suppl 7) Pages: 20-24
• [Journal Article] Gab1 is essential for postnatal a ngiogenesis via hepatocyte growth factor/ c-Met signaling (2011)
  • Author(s): Shioyama W, Nakaoka Y
  • Journal Title: Circ Res Volume: 108 Pages: 664-675
  • Peer Reviewed
• [Journal Article] Sildenafil and steroid thera py effectively improved POEMS syndrom e-associated pulmonary arterial hypertensi on (2011)
  • Author(s): Shimomura Y, Hara M, Mizote I, Nakaoka Y, Tanaka H, Asano Y, Sakata Y, Komuro I
  • Journal Title: International Journal of Hematology Volume: 92 Pages: 774-776
  • Peer Reviewed
• [Journal Article] A case of non-cardiogenic acute pulmonary edem a in a patient with POEMS syndrome-ass ociated pulmonary arterial hypertension (2011)
  • Author(s): Hara M, Mizote I, Nakaoka Y, Tanaka H, Asano Y, Sakata Y, Komuro I
  • Journal Title: A nn Hematol Volume: 90 Pages: 489-90
  • Peer Reviewed
• [Journal Article] 冠動脈疾患研究・治療の進歩と今後の課題 (2011)
  • Author(s): 中岡良和、小室一成
  • Journal Title: 日本臨床 Volume: 69(Suppl 7) Pages: 20-24
• [Journal Article] Gab1 is essential for postnatal angiogenesis via hepatocyte growth factor/c-Met signaling. (2011)
  • Author(s): Shioyama W, Nakaoka Y, Higuchi K, Minami T, Taniyama Y, Nishida K, Kidoya H, Sonobe T, Naito H, Arita Y, Hashimoto T, Kuroda T, Fujio Y, Shirai M, Takakura N, Morishita R, Yamauchi-Takihara K, Kodama T, Hirano T, Mochizuki N, Komuro I (co-corresponding author)
  • Journal Title: Circulation Research Volume: 108(Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Pulmonary arterial hypertension associated with chronic active Epstein-Barr virus infection. (2011)
  • Author(s): Hashimoto T, Sakata Y, Fukushima K, Maeda T, Arita Y, Shioyama W, Nakaoka Y, Hori Y, Morii E, Aozasa K, Kanakura Y, Yamauchi-Takihara K, Komuro I.
  • Journal Title: Internal Medicine Volume: 50 Pages: 119-24
  • NAID: 130000413209
  • Peer Reviewed
• [Journal Article] SHP2 mediates gp130-dependent cardiomyocyte hypertrophy via negative regulation of skeletalα-actin gene (2010)
  • Author(s): Nakaoka Y
  • Journal Title: J Mol Cell Cardiol Volume: 49 Pages: 157-164
  • Peer Reviewed
• [Journal Article] Yamauchi-Takihara K. The efficacy of tocilizumab i n a patient with pulmonary arterial hyper tension associated with Castleman' s diseas e (2010)
  • Author(s): Arita Y, Sakata Y, Sudo T, Maeda T, Ma tsuoka K, Tamai K, Higuchi K, Shioyam a W, Nakaoka Y, Kanakura Y
  • Journal Title: Heart Vessels Volume: 25 Pages: 444-7
  • Peer Reviewed
• [Journal Article] Therapeutic activation of STAT3 by I nterleukin-11 ameliorates cardiac fibrosis after myocardial infaraction (2010)
  • Author(s): Obana M, Maeda M, Takeda K, Hayama A, Mohri T, Yamashita T, Nakaoka Y, Takeda K, Matsumiya G, Azuma J, Fujio Y
  • Journal Title: Circulation Volume: 121 Pages: 684-691
  • Peer Reviewed
• [Journal Article] Angiopoietin-1の心血管系での役割 (2010)
  • Author(s): 中岡良和
  • Journal Title: 循環器内科 Volume: 67(2) Pages: 178-184
• [Journal Article] 心腎連関と内皮機能 (2010)
  • Author(s): 中岡良和、小室一成
  • Journal Title: 腎と透析 Volume: 69(4) Pages: 422-426
• [Journal Article] Sildenafil and steroid therapy effectively improved POEMS syndrome-associated pulmonary arterial hypertension. (2010)
  • Author(s): Shimomura Y, Hara M, Mizote I, Nakaoka Y, Tanaka H, Asano Y, Sakata Y, Komuro I.
  • Journal Title: International Journal of Hematology Volume: 92 Pages: 774-6
  • NAID: 10027674619
  • Peer Reviewed
• [Journal Article] A case of non-cardiogenic acute pulmonary edema in a patient with POEMS syndrome-associated pulmonary arterial hypertension (2010)
  • Author(s): Hara M, Mizote I, Nakaoka Y, Tanaka H, Asano Y, Sakata Y, Komuro I
  • Journal Title: Annals of Hematology Volume: 90(Epub ahead of print)
  • Peer Reviewed
• [Journal Article] SHP2 mediates gp130-dependent cardiomyocyte hypertrophy via negative regulation of skeletal alpha-actin gene. (2010)
  • Author(s): Nakaoka Y, Shioyama W, Kunimoto S, Arita Y, Higuchi K, Yamamoto K, Fujio Y, Nishida K, Kuroda T, Hirota H, Yamauchi-Takihara K, Hirano T, Komuro I, Mochizuki N.
  • Journal Title: Journal of Molecular and Cellular Cardiology Volume: 49 Pages: 157-164
  • Peer Reviewed
• [Journal Article] SHP2 mediates gp130-dependent cardiomyocyte hypertrophy via negative regulation of skeletal alpha-actin gene (2010)
  • Author(s): Nakaoka Y, Shioyama W, Arita Y, Higuchi K, Kunimoto S, Fujio Y, Nishida K, Kuroda T, Hirota H, Yamauchi-Takihara K, Komuro I, Mochizuki N.
  • Journal Title: Journal of Molecular and Cellular Cardiology (in press)
  • Peer Reviewed
• [Journal Article] Therapeutic activation of Signal Transducer and Activator of Transcription 3 by Interleukin-11 Ameriolates Cardiac Fibrosis After Myocardial Infarction (2010)
  • Author(s): Obana M, Maeda M, Takeda K, Hayama A, Mohri T, Yamashita T, Nakaoka Y, Takeda K, Matsumiya G, Azuma J, Fujio Y
  • Journal Title: Circulation 121 Pages: 684-391
  • Peer Reviewed
• [Journal Article] Angiopoietin-1の心血管系での役割 (2010)
  • Author(s): 中岡良和
  • Journal Title: 循環器内科 (in press)
• [Journal Article] R ao GN. A role for Gab1/ SHP2 in thromb in activation of PAK1 : gene transfer of k inase-dead PAK1 inhibits injury-induced r estenosis (2009)
  • Author(s): Wang D, Paria BC, Zhang Q, Karpurapu M, Li Q, Gerthoffer WT, Nakaoka Y
  • Journal Title: Circ Res Volume: 104 Pages: 1066-75
  • Peer Reviewed
• [Journal Article] Clinical sig nificance of plasma endothelin-1 level aft er bosentan administration in pulmonary arterial hypertension (2009)
  • Author(s): Hiramoto Y, Shioyama W, Higuchi K, Ar ita Y, Kuroda T, Sakata Y, Nakaoka Y, Fujio Y, Yamauchi-Takihara K
  • Journal Title: J Cardiol Volume: 53 Pages: 374-80
  • NAID: 10025183776
  • Peer Reviewed
• [Journal Article] 心血管調節因子: Neuregul in-1とAngiopoietin-1が形成するパラクラインシグナルネットワーク (2009)
  • Author(s): 中岡良和
  • Journal Title: 心血管調節因子: Neuregul in-1とAngiopoietin-1が形成するパラクラインシグナルネットワーク Volume: 41 Pages: 1298-1301
• [Journal Article] A role for Gab1/SHP2 in thrombin activation of PAK1 : gene transfer of kinase-dead PAK1 inhibits injury-induced restenosis (2009)
  • Author(s): Wang D, Paria BC, Zhang Q, Karpurapu M, Li Q, Gerthoffer WT, Nakaoka Y, Rao GN.
  • Journal Title: Circulation Research 104 Pages: 1066-75
  • Peer Reviewed
• [Journal Article] 心血管調節因子 : Neuregulin-1と Angiopoietin-1が形成する心臓パラクラインシグナルネットワーク (2009)
  • Author(s): 中岡良和
  • Journal Title: 心臓 41 Pages: 1298-1301
  • NAID: 130003376832
• [Presentation] Blockade of interleukin-6 Signaling Prevents Hypoxia-induced Pulmonary Arterial Hypertension in Mice (2011)
  • Author(s): Hashimoto T, Nakaoka Y, Sonobe T, Arita Y, Ikeoka K, Shirai M, Komuro I
  • Organizer: 第19回日本血管生物医学会学術集会
  • Place of Presentation: 東京ステーションコンファレンス(東京都)
  • Year and Date: 2011-12-09
• [Presentation] Blockade of interleukin-6 Signaling Prevents Hypoxia-induced Pulmonary Arterial Hypertension in Mice (2011)
  • Author(s): Takahiro Hashimoto, Yoshikazu Nakaoka, Takashi Sonobe, Yoh Arita, Kuniyasu Ikeoka, Mikiyasu Shirai, Issei Komuro
  • Organizer: 第19回日本血管生物医学会学術集会
  • Place of Presentation: 東京ステーションコンファレンス(東京都)(ポスター発表)
  • Year and Date: 2011-12-09
• [Presentation] Endothelial Gab1Deletion Accelerates Angiotensin II-Dependent Vascular Inflammation and Atherosclerosis in ApoE Knockout Mice (2011)
  • Author(s): Yoshikazu Nakaoka, Kaori Higuchi, Wataru Shimoyama, Yoh Arita, Takahiro Hashimoto, Tadashi Kuroda, Yasushi Fujio, Keiko Takihara, Issei Komuro
  • Organizer: 第28回ISHR日本部会総会
  • Place of Presentation: 学術総合センター(東京都)(ポスター発表)
  • Year and Date: 2011-12-03
• [Presentation] 心筋から分泌されるアンジオポイエチン1は冠静脈の形成に必須である (2011)
  • Author(s): 有田陽、中岡良和、白井学、有馬勇一郎、樋口香織、橋本崇弘、池岡邦泰、安居琢、瀧原圭子、西山功一、山岸敬幸、栗原裕基、小室一成
  • Organizer: 第2回MCC II
  • Place of Presentation: ホテルピアノ(北海道余市郡赤井川村)
  • Year and Date: 2011-09-04
• [Presentation] 心筋から分泌されるアンジオポイエチン1は冠静脈の形成に必須である (2011)
  • Author(s): 有田陽、中岡良和、白井学、有馬勇一郎、樋口香織、橋本崇弘、池岡邦泰、安居琢、瀧原圭子、西山功一、山岸敬幸、栗原裕基、小室一成
  • Organizer: 第2回Molecular Cardiovascular Conerence II
  • Place of Presentation: ホテルピアノ(北海道余市郡赤井川村)(口頭発表)
  • Year and Date: 2011-09-04
• [Presentation] Gab1 is an essential component for postnatal angiogenesis after ischemia via HGF/ c-Met signaling (2011)
  • Author(s): Nakaoka Y
  • Organizer: The 9th Japan-Korea Joint Symposium on Vascular Biology 2011
  • Place of Presentation: 釜山ウェスティンホテル(韓国・釜山)
  • Year and Date: 2011-08-26
• [Presentation] Gab1 is an essential component for postnatal angiogenesis after ischemia via HGF/c-Met signaling (2011)
  • Author(s): Yoshikazu Nakaoka
  • Organizer: The 9th Japan-Korea Joint Symposium on Vascular Biology 2011
  • Place of Presentation: 釜山ウェスティンホテル(韓国・釜山)(招待講演Young Faculty Symposium on Vascular Biology)
  • Year and Date: 2011-08-26
• [Presentation] Gab1 Negatively regulates Angiotensin II-accelerated Atherosclerosis in Apolipoprotein E Deficient Mice (2011)
  • Author(s): Nakaoka Y, Higuchi K, Shioyama W, Taniyama Y, Arita Y, Hashimoto T, Fujio Y, Yamauchi-Takihara K, Morishita R, Hirano T, Komuro I
  • 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(横浜市)
  • Year and Date: 2011-08-04
• [Presentation] Gab1 Negatively regulates Angiotensin II-accelerated Atherosclerosis in Apolipoprotein E Deficient Mice (2011)
  • Author(s): Yoshikazu Nakaoka, Kaori Higuchi, Wataru Shioyama, Yoshiaki Taniyama, Yoh Arita, Takahiro Hashimoto, Yasushi Fujio, Keiko Yamauchi-Takihara, Ryuichi Morishita, Toshio Hirano, Issei Komuro
  • 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(横浜市)(Featured Research Session)
  • Year and Date: 2011-08-04
• [Presentation] The Role of Gab Familyl Docking Proteins in the Pathophysiology of the Cardiovascular Diseases (2011)
  • Author(s): Nakaoka Y
  • Organizer: The 12th US-Japan-Asia Dialogue on Cardiovascular Diseases and Young Investigator Competition(Pfizer)
  • Place of Presentation: 高輪プリンスホテル(東京都)
  • Year and Date: 2011-07-31
• [Presentation] The Role of Gab Familyl Docking Proteins in the Pathophysiology of the Cardiovascular Diseases (2011)
  • Author(s): Yoshikazu Nakaoka
  • Organizer: The 12th US-Japan-Asia Dialogue on Cardiovascular Diseases and Young Investigator Competition (Pfizer)
  • Place of Presentation: 高輪プリンスホテル(東京都)(Keynote Lecture)(招待講演)
  • Year and Date: 2011-07-31
• [Presentation] Gab1 is Critically involved in HGF-dependent Postnatal Angiogenesis after ischemia (2011)
  • Author(s): Shioyama W, Nakaoka Y, Higuchi K, Minami T, Nishida K, Taniyama Y, Kidoya H, Arita Y, Hashimoto T, Fujio Y, Shirai M, Takakura N, Morishita R, Yamauchi-Takihara K, Kodama T, Hirano T, Mochizuki N, Komuro I
  • Organizer: 日本循環器学会
  • Place of Presentation: 京都国際会館(京都府)
  • Year and Date: 2011-03-15
• [Presentation] Gab1 is Critically involved in HGF-dependent Postnatal Angiogenesis after ischemia. (2011)
  • Author(s): Wataru Shioyama
  • Organizer: 日本循環器学会
  • Place of Presentation: Chicago, IL, USA
  • Year and Date: 2011-03-15
• [Presentation] Gab1 Negatively regulates Angiotensin II-accelerated Atherosclerosis in Apolipoprotein E Deficient Mice (2010)
  • Author(s): Higuchi K, Nakaoka Y, Shioyama W, TaniyamaY, Arita Y, Hashimoto T, Fujio Y, Yamauchi-Takihara K, Morishita R, Hirano T, Komuro I
  • Organizer: 2010 American Heart Association Scientific Sessions
  • Place of Presentation: 米国・シカゴ
  • Year and Date: 2010-11-15
• [Presentation] Gab1 Attenuates Angiotensin II-accelerated Atherosclerosis and Vascular Remodeling in Apolipoprotein E Deficient Mice via HGF/c-Met Signaling Pathway (2010)
  • Author(s): Kaori Higuchi
  • Organizer: 2010 American Heart Association Scientific Sessions
  • Place of Presentation: Chicago, IL, USA
  • Year and Date: 2010-11-15
• [Presentation] SHP2 mediates gp130-dependent cardiomyocyte hypertrophy via negative regulation of skeletal alpha-actin gene (2010)
  • Author(s): Nakaoka Y
  • Organizer: Basic Cardiovascular Sciences 2010 American Heart Association Scientific Sessions
  • Place of Presentation: 米国・カリフォルニア州、Rancho Mirage
  • Year and Date: 2010-07-20
• [Presentation] SHP2 mediates gp130-dependent cardiomyocyte hypertrophy via negative regulation of skeletal alpha-actin gene (2010)
  • Author(s): Yoshikazu Nakaoka
  • Organizer: Basic Cardiovascular Sciences 2010 American Heart Association Scientific Sessions
  • Place of Presentation: Rancho Mirage, CA, USA
  • Year and Date: 2010-07-20
• [Presentation] Interaction of Docking Protein Gab1 with Tyrosine Phosphatase SHP2 Regulates Hepatocyte Growth Factor-dependent ERK5 Activation and Upregulation of Kruppel-like Factor 2 in the Vascular Endothelium (2009)
  • Author(s): Shioyama W., Nakaoka Y. Higuchi K, Minami T, Nishida K, Taniyama Y, Kidoya H, Arita Y, Hashimoto T, Fujio Y, Shirai M, Takakura N, Morishita R, Yamauchi-Takihara K, Kodama T, Hirano T, Mochizuki N, Komuro I
  • Organizer: American Heart Association, Scientific Sessions 2009
  • Place of Presentation: Orange County ConventionCenter(米国・フロリダ州オーランド)
  • Year and Date: 2009-11-18
• [Presentation] Interaction of Docking Protein Gab1 with Tyrosine Phosphatase SHP2 Regulates Hepatocyte Growth Factor-dependent ERK5 Activation and Upregulation of Kruppel-like Factor 2 in the Vascular Endothelium (2009)
  • Author(s): Shioyama W., Nakaoka Y., et al.
  • Organizer: American Heart Association, Scientific Sessions 2009
  • Place of Presentation: Orange County Convention Center, Orlando, FL, USA
  • Year and Date: 2009-11-18
• [Presentation] Scaffolding Docking Protein Gab1 Has an Essential Role for HGF-dependent Endothelial Signaling and Angiogenesis after Hindlimb Ischemia (2009)
  • Author(s): Nakaoka Y. Shioyama W., Higuchi K, Minami T, Nishida K, Taniyama Y, Kidoya H, Arita Y, Hashimoto T, Fujio Y, Shirai M, Takakura N, Morishita R, Yamauchi-Takihara K, Kodama T, Hirano T, Mochizuki N, Komuro I
  • Organizer: Basic Cardiovascular Sciences Conference 2009 : Molecular Mechanisms of Cardiovascular Disease
  • Place of Presentation: The Ritz-Carlton in Lake Las Vegas,米国ネバダ州ラスベガス)
  • Year and Date: 2009-07-22
• [Presentation] Scaffolding Docking Protein Gab1 Has an Essential Role for HGF-depen dent Endothelial Signaling and Angiogenesis after Hindlimb Ischemia (2009)
  • Author(s): Nakaoka Y., et al.
  • Organizer: Basic Cardiovascular Sciences Conference 2009 : Molecular Mechanisms of Cardiovascular Disease
  • Place of Presentation: The Ritz-Carlton in Lake Las Vegas, NV, USA
  • Year and Date: 2009-07-22
• [Book] 血管生物医学事典 (2011)
  • Author(s): 小室一成・中岡良和, 他
  • Publisher: 朝倉書店
• [Book] 血管生物医学事典(分担執筆:3項目合計9ページ) (2011)
  • Author(s): 中岡良和、小室一成
  • Total Pages: 489
  • Publisher: 朝倉書店
• [Remarks]
  • URL: http://www.med.osaka-u.ac.jp/pub/cardiology/27research/2784res.html
• [Remarks]
  • URL: http://www.med.osaka-u.ac.jp/pub/cardiology/27research/2784res.html
• [Remarks]
  • URL: http://www.med.osaka-u.ac.jp/pub/cardiology/27research/2784res.html
• [Remarks]
  • URL: http://www.med.osaka-u.ac.jp/pub/cardiology/27research/2781res.html