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Elucidating molecular mechanism of thrombin signaling involved in pathogenesis and progression of pulmonary hypertension

Research Project

Project/Area Number 25860632
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Cardiovascular medicine
Research Institution独立行政法人国立病院機構岡山医療センター(臨床研究部)

Principal Investigator

OGAWA Aiko  独立行政法人国立病院機構岡山医療センター(臨床研究部, その他部局等, その他 (40572748)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords肺高血圧 / 平滑筋細胞 / トロンビン / 細胞内カルシウム / シグナル伝達
Outline of Final Research Achievements

To elucidate the role of thrombin signaling in pathogenesis and progression of pulmonary hypertension, we performed the present study by using lung tissues and isolated pulmonary arterial smooth muscle cells from patients with pulmonary hypertension. Protease activated receptor 1 (PAR1), which acts as a thrombin receptor, was highly expressed in pulmonary arterial smooth muscle cells from patients with pulmonary hypertension. We demonstrated that thrombin/PAR1 signaling and its downstream pathways (Akt/mTOR signaling and p38 signaling) play important roles in progression of pulmonary vascular remodeling. These results indicate that thrombin and its downstream signaling pathways may be novel therapeutic targets in pulmonary hypertension.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (29 results)

All 2015 2014 2013 2011

All Journal Article (12 results) (of which Peer Reviewed: 11 results,  Open Access: 1 results) Presentation (17 results) (of which Invited: 4 results)

  • [Journal Article] Balloon pulmonary angioplasty: a treatment option for inoperable patients with chronic thromboembolic pulmonary hypertension2015

    • Author(s)
      Ogawa A, Matsubara H.
    • Journal Title

      frontiers in CARDIOVASCULAR MEDECINE.

      Volume: 2 Pages: 1-7

    • DOI

      10.3389/fcvm.2015.00004

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Treatment of idiopathic/hereditary pulmonary arterial hypertension.2014

    • Author(s)
      Matsubara H, Ogawa A.
    • Journal Title

      J Cardiol.

      Volume: 64 Issue: 4 Pages: 243-9

    • DOI

      10.1016/j.jjcc.2014.06.009

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Letter by Ogawa and Matsubara regarding article, "Anticoagulation and survival in pulmonary arterial hypertension: results from the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA)".2014

    • Author(s)
      Ogawa A, Matsubara H.
    • Journal Title

      Circulation.

      Volume: 130 Issue: 12

    • DOI

      10.1161/circulationaha.114.009780

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Histological changes of pulmonary arteries treated by balloon pulmonary angioplasty in a patient with chronic thromboembolic pulmonary hypertension.2014

    • Author(s)
      Kitani M, Ogawa A, Sarashina T, Yamadori I, Matsubara H.
    • Journal Title

      Circ Cardiovasc Interv.

      Volume: 7 Issue: 6 Pages: 857-9

    • DOI

      10.1161/circinterventions.114.001533

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 慢性血栓塞栓性肺高血圧症:治療と研究の進歩2014

    • Author(s)
      小川 愛子、 松原 広己
    • Journal Title

      日本心脈管作動物質学会機関誌「血管」

      Volume: 37 Pages: 99-106

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Long-term patient survival with idiopathic/heritable pulmonary arterial hypertension treated at a single center in Japan.2014

    • Author(s)
      Ogawa A, Ejiri K, Matsubara H.
    • Journal Title

      Life Sci.

      Volume: in press Issue: 2 Pages: 414-419

    • DOI

      10.1016/j.lfs.2014.01.077

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pulmonary Microvascular Remodeling after Balloon Pulmonary Angioplasty in a Patient with Chronic Thromboembolic Pulmonary Hypertension2014

    • Author(s)
      Ogawa A, Kitani M, Mizoguchi H, Munemasa M, Matsuo K, Yamadori I, Andou A, Matsubara H.
    • Journal Title

      Internal Medicine

      Volume: 53 Issue: 7 Pages: 729-733

    • DOI

      10.2169/internalmedicine.53.1343

    • NAID

      130003392735

    • ISSN
      0918-2918, 1349-7235
    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Imatinib is Partially Effective for the Treatment of Pulmonary Capillary Hemangiomatosis2014

    • Author(s)
      Adachi S, Hirashiki A, Kondo T, Nakaguro M, Ogawa A, Miyaji K, Matsubara H, Yokoi T, Murohara T.
    • Journal Title

      Internal Medicine

      Volume: 53 Issue: 6 Pages: 603-607

    • DOI

      10.2169/internalmedicine.53.1157

    • NAID

      130003392705

    • ISSN
      0918-2918, 1349-7235
    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pulmonary Tumor Thrombotic Microangiopathy with Circulatory Failure Treated with Imatinib2013

    • Author(s)
      Ogawa A, Yamadori I, Matsubara O, Matsubara H.
    • Journal Title

      Internal Medicine

      Volume: 52 Issue: 17 Pages: 1927-1930

    • DOI

      10.2169/internalmedicine.52.0718

    • NAID

      130003365790

    • ISSN
      0918-2918, 1349-7235
    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Importance of differential diagnosis of pulmonary hypertension.2013

    • Author(s)
      Ogawa A.
    • Journal Title

      Journal of Cardiology Cases

      Volume: na

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Different sizes of centrilobular ground-glass opacities in chest high-resolution computed tomography of patients with pulmonary veno-occlusive disease and patients with pulmonary capillary hemangiomatosis2013

    • Author(s)
      Miura A, Akagi S, Nakamura K, Ohta-Ogo K, Hashimoto K, Nagase S, Kohno K, Kusano K, Ogawa A, Matsubara H, Toyooka S, Oto T, Ohtsuka A, Ohe T, Ito H
    • Journal Title

      Cardiovasc Pathol

      Volume: 22 Issue: 4 Pages: 287-293

    • DOI

      10.1016/j.carpath.2012.12.002

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Prostaglandin I(2) induces apoptosis via upregulation of Fas ligand in pulmonary artery smooth muscle cells from patients with idiopathic pulmonary arterial hypertension2011

    • Author(s)
      Akagi S, Nakamura K, Matsubara H, Fukushima Kusano K, Kataoka N, Oto T, Miyaji K, Miura A, Ogawa A, Yoshida M, Ueda-Ishibashi H, Yutani C, Ito H
    • Journal Title

      Int J Cardiol

      Volume: in press Issue: 3 Pages: 499-505

    • DOI

      10.1016/j.ijcard.2011.09.004

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] トロンビンシグナル阻害による慢性血栓塞栓性肺高血圧症の新たな治療法の可能性2015

    • Author(s)
      小川 愛子、松原 広己
    • Organizer
      第44回日本心脈管作動物質学会
    • Place of Presentation
      高松センタービル(香川県)
    • Year and Date
      2015-02-06
    • Related Report
      2014 Annual Research Report
  • [Presentation] PVODの臨床診断2014

    • Author(s)
      小川 愛子
    • Organizer
      第2回日本肺高血圧学会(JPHS)第3回日本肺循環学会(JPCS)合同学術集会
    • Place of Presentation
      大手町サンケイプラザ(東京都)
    • Year and Date
      2014-10-04
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Role of Thrombin in Vascular Remodeling in Chronic Thromboembolic Pulmonary Hypertension2014

    • Author(s)
      Ogawa A, Ariyasu S, Shinno Y, Yamadori I, Matsubara H, Yuan JX
    • Organizer
      International CTEPH Conference 2014
    • Place of Presentation
      Institut Des Cordeliers(フランス)
    • Year and Date
      2014-06-02
    • Related Report
      2014 Annual Research Report
  • [Presentation] Increased platelet-derived microparticle levels in patients with pulmonary hypertension2014

    • Author(s)
      Ogawa A, Tsukuda S, Sato S, Miyaji K, Munemasa M, Matsubara H
    • Organizer
      The 18th International Vascular Biology Meeting
    • Place of Presentation
      みやこめっせ(京都府)
    • Year and Date
      2014-04-15
    • Related Report
      2014 Annual Research Report
  • [Presentation] Trans-catheter Treatment of Reperfusion Pulmonary Injury during Balloon Pulmonary Angioplasty for Patients with Chronic Thromboembolic Pulmonary Hypertension2014

    • Author(s)
      Ejiri K, Minatsuki S, Nagayoshi S, Mizoguchi H, Ogawa A, Sahara S, Miyaji K, Miyaji K, Munemasa M, Matsubara H
    • Organizer
      第78回日本循環器学会学術総会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] Balloon Pulmonary Angioplasty would be a Cure for Chronic Thromboembolic Pulmonary Hypertension―Hemodynamic and Angiographical Assessments after Long-Term Follow Up―2014

    • Author(s)
      Tabuchi I, Ejiri K, Nagayoshi S, Mizoguchi H, Ogawa A, Munemasa M, Matsubara H
    • Organizer
      第78回日本循環器学会学術総会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] IVUS Guided Balloon Pulmonary Angioplasty Diminished Reperfusion Pulmonary Injury by Suppressing Pressure Overload to Distal Pulmonary Arteries2014

    • Author(s)
      Nagayoshi S, Minatsuki S, Mizoguchi H, Ogawa A, Munemasa M, Matsubara H.
    • Organizer
      第78回日本循環器学会学術総会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] PVOD/PCH臨床診断スコア2013

    • Author(s)
      小川 愛子、 宗政 充、 宮地克維、 松原広己
    • Organizer
      第53回日本呼吸器学会学術講演会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] Molecular Mechanisms for Development of Pulmonary Vascular Remodeling in Chronic Thromboembolic Pulmonary Hypertension2013

    • Author(s)
      小川 愛子
    • Organizer
      Japanese Pulmonary Circulation society, 2nd Scientific Meeting
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Pulmonary Vascular Remodeling in Pulmonary Hypertension2013

    • Author(s)
      小川 愛子
    • Organizer
      EMBC 2013
    • Place of Presentation
      大阪
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension2013

    • Author(s)
      小川 愛子
    • Organizer
      EMBC 2013
    • Place of Presentation
      大阪
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Clinical prediction rule for identifying patients with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis2013

    • Author(s)
      Ogawa A, Miyaji K, Matsubara H.
    • Organizer
      ESC2013
    • Place of Presentation
      オランダ
    • Related Report
      2013 Research-status Report
  • [Presentation] Long-term survival in Japanese patients with idiopathic/heritable pulmonary arterial hypertension2013

    • Author(s)
      Ogawa A, Miyaji K, Matsubara H.
    • Organizer
      The Thirteenth International Conference on Endothelin
    • Place of Presentation
      Tokyo
    • Related Report
      2013 Research-status Report
  • [Presentation] 門脈肺高血圧症の特徴と治療効果について2013

    • Author(s)
      江尻 健太郎、 溝口 博喜、 小川 愛子、 宮地 克維、 宗政 充、 松原 広己
    • Organizer
      第61回日本心臓病学会学術集会
    • Place of Presentation
      熊本
    • Related Report
      2013 Research-status Report
  • [Presentation] 特発性/遺伝性肺動脈性肺高血圧症の長期予後と関連する因子の検討2013

    • Author(s)
      小川愛子、 佐藤 徹、 田村雄一、 松原広己
    • Organizer
      第61回日本心臓病学会学術集会
    • Place of Presentation
      熊本
    • Related Report
      2013 Research-status Report
  • [Presentation] 急性静脈血栓塞栓症に対するフォンダパリヌクスの使用経験2013

    • Author(s)
      上枝 弘雄、 宗政 充、 江尻 健太郎、小川 愛子、 宮地 克維、 松原 広己
    • Organizer
      第61回日本心臓病学会学術集会
    • Place of Presentation
      熊本
    • Related Report
      2013 Research-status Report
  • [Presentation] 肺静脈閉塞症/肺毛細血管腫症の臨床的特徴2013

    • Author(s)
      小川愛子、 宮地克維、 宗政 充、 松原広己
    • Organizer
      第67回国立病院総合医学会
    • Place of Presentation
      石川
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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