Cyclophilin A Mediates Pulmonary Vascular Remodeling by Rho-kinase Activation in Patients with Pulmonary Hypertension

• Project/Area Number: 21790698
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Circulatory organs internal medicine
• Research Institution: Tohoku University
• Principal Investigator: SATOH Kimio Tohoku University, 大学院・医学系研究科, 助教 (80436120)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 酸化ストレス / 肺高血圧 / 血管平滑筋細胞 / 低酸素 / 低酸素ストレス / 大動脈瘤 / 心不全 / 心肥大

Research Abstract

We tested the hypothesis that CyPA contributes to pulmonary vascular remodeling in PAH patients. Our results provide the direct evidence that the CyPA/Rho-kinase pathway plays an important role in the pathogenesis of PAH in humans.

Research Products

• [Journal Article] Rho-kinase : important new therapeutic target in cardiovascular diseases. (2011)
  • Author(s): Satoh K, Fukumoto Y, Shimokawa H.
  • Journal Title: Am J Physiol Heart Circ Physiol. in press
  • Peer Reviewed
• [Journal Article] Vascular-derived reactive oxygen spiecies for homeostasis and diseases. (2011)
  • Author(s): Satoh K, Berk BC, Shimokawa H.
  • Journal Title: Nitric Oxide in press
  • Peer Reviewed
• [Journal Article] Emergence of the Erythropoietin /Erythropoietin Receptor System as a Novel Cardiovascular Therapeutic Target. (2011)
  • Author(s): Satoh K, Fukumoto Y, Nakano M, Kagaya Y, Shimokawa H.
  • Journal Title: Journal of Cardiovascular Pharmacology in press
  • Peer Reviewed
• [Journal Article] Cyclophilin A is an inflammatory mediator that promotes atherosclerosis in apolipoprotein E-deficient mice. (2011)
  • Author(s): Nigro P, Satoh K, O'Dell MR, Soe NN, Cui Z, Mohan A, Abe J, Alexis J, Sparks JD, Berk BC.
  • Journal Title: Journal of Experimental Medicine. 208(*equal contribution) Pages: 53-66
  • Peer Reviewed
• [Journal Article] Cyclophilin A promotes cardiac hypertrophy in apolipoprotein E-deficient mice. (2011)
  • Author(s): Satoh K, Nigro P, Zeidan A, Soe NN, Jaffre F, Oikawa M, O'Dell MR, Cui Z, Menon P, Lu Y, Mohan A, Yan C, Blaxall BC, Berk BC.
  • Journal Title: Arterioscler Thromb Vasc Biol. 31 Pages: 1116-1123
  • Peer Reviewed
• [Journal Article] Cyclophilin A Promotes Cardiac Hypertrophy in Apolipoprotein E-Deficient Mice. (2011)
  • Author(s): Satoh K
  • Journal Title: Arterioscler Thromb Vase Biol. Volume: 31 Pages: 1116-1123
  • Peer Reviewed
• [Journal Article] Cyclophilin A is an inflammatory mediator that promotes atheroscl erosis in apolipoprotein E-deficient mice. (2011)
  • Author(s): Nigro P, Satoh K
  • Journal Title: Journal of Experimental Medicine. Volume: 208 Pages: 53-66
  • Peer Reviewed
• [Journal Article] Vascular-derived reactive oxygen spiecies for homeostasis and diseases. (2011)
  • Author(s): Satoh K, Shimokawa H
  • Journal Title: Nitric Oxide Volume: 24(印刷中)
  • Peer Reviewed
• [Journal Article] Emergence of the Erythropoietin/Erythropoietin Receptor System as a Novel Cardiovascular Therapeutic Target (2011)
  • Author(s): Satoh K, Shimokawa H
  • Journal Title: Journal of cardiovascular pharmacology Volume: 57(印刷中)
  • Peer Reviewed
• [Journal Article] 血管と酸化ストレス (2011)
  • Author(s): 佐藤公雄
  • Journal Title: Angiotensin Research Volume: 8(印刷中)
• [Journal Article] Cyclophilin A : a promising new target in cardiovascular therapy. (2010)
  • Author(s): Satoh K, Shimokawa H, Berk BC.
  • Journal Title: Circulation J 74(review) Pages: 2249-2256
  • NAID: 10026972151
  • Peer Reviewed
• [Journal Article] Oxidative stress and vascular smooth muscle cell growth : A mechanistic linkage by cyclophilin A. (2010)
  • Author(s): Satoh K, Nigro P, Berk BC.
  • Journal Title: Antioxidants & Redox Signaling 12 Pages: 675-682
  • Peer Reviewed
• [Journal Article] Cyclophilin A : a promising new target in cardiovascular therapy. (2010)
  • Author(s): Satoh K, Shimokawa H
  • Journal Title: Circulation J Volume: 74 Pages: 2249-2256
  • NAID: 10026972151
  • Peer Reviewed
• [Journal Article] Oxidative stress and vascular smooth muscle cell growth : A mechanistic linkage by cyclophilin A. (2010)
  • Author(s): Satoh K
  • Journal Title: Antioxidants & Redox Signaling Volume: 12 Pages: 675-682
  • Peer Reviewed
• [Journal Article] PKCζ decreases eNOS protein stability via inhibitory phosphorylation of ERK5. (2010)
  • Author(s): Nigro P
  • Journal Title: Blood Volume: 116 Pages: 1971-1979
  • Peer Reviewed
• [Journal Article] Identification of new prognostic factors of pulmonary hypertension. (2010)
  • Author(s): Miura Y
  • Journal Title: Circulation J Volume: 74 Pages: 1965-1971
  • Peer Reviewed
• [Journal Article] Optical coherence tomography as a novel diagnostic tool for distal type chronic thromboembolic pulmonary hypertension. (2010)
  • Author(s): Tatebe S
  • Journal Title: Circulation J Volume: 74 Pages: 1742-1744
  • Peer Reviewed
• [Journal Article] エリスロポエチンと酸化ストレス応答性サイクロフィリンA (2010)
  • Author(s): 佐藤公雄, 下川宏明
  • Journal Title: Vascular Medicine Volume: 6 Pages: 1-10
  • Peer Reviewed
• [Journal Article] Oxidative stress and vascular smooth muscle cell growth : A mechanistic linkage by cyclophilin A (2010)
  • Author(s): Satoh K, et al.
  • Journal Title: Antioxidants & Redox Signaling 12 Pages: 675-682
  • Peer Reviewed
• [Journal Article] Cyclophilin A enhances vascular oxidative stress and the development of angiotensin II-induced aortic aneurysms. (2009)
  • Author(s): Satoh K, Nigro P, Matoba T, O'Dell MR, Mohan A, Yan C, Illig KA, Berk BC.
  • Journal Title: Nature Medicine 15 Pages: 649-656
  • Peer Reviewed
• [Journal Article] Statin ameliorates hypoxia-induced pulmonary hypertension associated with down-regulated stromal cell-derived factor-1. (2009)
  • Author(s): Satoh K, Fukumoto Y, Nakano M, Ishii N, Sugamura K, Shimokawa H.
  • Journal Title: Cardiovascular Research 81 Pages: 226-234
  • Peer Reviewed
• [Journal Article] Cyclophilin A enhances vascular oxidative stress and the development of angiotensin II-induced aortic aneurysms (2009)
  • Author(s): Satoh K, et al.
  • Journal Title: Nature Medicine 15 Pages: 649-656
  • Peer Reviewed
• [Journal Article] Statin ameliorates hypoxia-induced pulmonary hypertension associated with down-regulated stromal cell-derived factor-1 (2009)
  • Author(s): Satoh K, et al.
  • Journal Title: Cardiovascular Research 81 Pages: 226-234
  • Peer Reviewed
• [Presentation] 「新しい心血管疾患バイオマーカー」Cyclophilin A Is a Novel Biomarker for Aortic Aneurysms and Atherosclerotic Plaque Instability. (2011)
  • Author(s): 佐藤公雄
  • Organizer: 日本循環器学会・シンポジウム
  • Place of Presentation: 横浜
  • Year and Date: 2011-08-03
• [Presentation] Cyclophilin A is an inflammatory mediator that promotes atherosclerosis. Young Investigator's Award. (2010)
  • Author(s): 佐藤公雄
  • Organizer: アジア血管生物学学会・受賞講演
  • Place of Presentation: 香港
  • Year and Date: 2010-11-21
• [Presentation] Cyclophilin A is an inflammatory mediator that promotes atherosclerosis. (2010)
  • Author(s): 佐藤公雄
  • Organizer: Scientific Meeting of Asian Society for Vascular Biology, Young Investigator's Award.
  • Place of Presentation: 中国(香港)
  • Year and Date: 2010-11-21
• [Presentation] Emerging Importance of the Erythropoietin/Erythropoietin Receptor System and Cyclophilin A as Novel Therapeutic Targets in Cardiovascular Medicine. (2010)
  • Author(s): 佐藤公雄
  • Organizer: 4th Scientific Meeting of Asian Society for Vascular Biology 招待講演
  • Place of Presentation: 香港
  • Year and Date: 2010-11-20
• [Presentation] Emerging Importance of the Erythropoietin/Erythropoietin Receptor System and Cyclophilin A as Novel Therapeutic Targets in Cardiovascular Medicine. (2010)
  • Author(s): 佐藤公雄
  • Organizer: Scientific Meeting of Asian Society for Vascular Biology, Symposium.
  • Place of Presentation: 中国(香港)
  • Year and Date: 2010-11-20
• [Presentation] Cyclophilin A Mediates Pulmonary Vascular Remodeling by Rho-kinase Activation in Patients with Pulmonary Hypertension (2010)
  • Author(s): 佐藤公雄
  • Organizer: アメリカ心臓協会年次総会
  • Place of Presentation: アメリカ(シカゴ)
  • Year and Date: 2010-11-14
• [Presentation] Cyclophilin A : a potential molecular marker of instability of atherosclerotic plaque and abdominal aortic aneurysm. (2010)
  • Author(s): 佐藤公雄
  • Organizer: Visiting AstraZeneca Molndal R&D, Sweden 招待講演
  • Place of Presentation: ストックホルム
  • Year and Date: 2010-09-02
• [Presentation] Cyclophilin A : a potential molecular marker of instability of atherosclerotic plaque and abdominal aortic aneurysm. (2010)
  • Author(s): 佐藤公雄
  • Organizer: Visiting AstraZeneca Molndal R&D
  • Place of Presentation: スウェーデン(ストックホルム)
  • Year and Date: 2010-09-02
• [Presentation] Cyclophilin A mediates endothelial damage and promotes recruitment of inflammatory cells and atherosclerosis. (2010)
  • Author(s): 佐藤公雄
  • Organizer: 6th International Conference on the Biology, Chemistry, and Therapeutic Applications of Nitric Oxide. Young Investigator's Award 最優秀賞国際Nitric Oxide 学会賞・受賞講演
  • Place of Presentation: 京都
  • Year and Date: 2010-06-14
• [Presentation] Cyclophilin A mediates endothelial damage and promotes recruitment of inflammatory cells and atherosclerosis. (2010)
  • Author(s): 佐藤公雄
  • Organizer: 6th International Conference on the Biology, Chemistry, and Therapeutic Applications of Nitric Oxide. Young Investigator's Award
  • Place of Presentation: 京都
  • Year and Date: 2010-06-14
• [Presentation] Emerging Importance of the Erythropoietin/Erythropoietin Receptor System and Cyclophilin A as Novel Therapeutic Targets in Cardiovascular Medicine. Young Investigator's Award. (2010)
  • Author(s): 佐藤公雄
  • Organizer: 日本循環器学会賞・受賞講演
  • Place of Presentation: 京都
  • Year and Date: 2010-03-05
• [Presentation] Cyclophilin A Augments ROS production and Angiotensin II-induced Cardiac Hypertrophy in Mice.American Heart Association, Melvin L.Marcus Young Investigator's Award. (2009)
  • Author(s): 佐藤公雄
  • Organizer: アメリカ心臓協会学会賞・受賞講演
  • Place of Presentation: 米国オーランド
  • Year and Date: 2009-11-15
• [Presentation] Melvin L.Marcus Young Investigator Award (2009)
  • Author(s): Kimio Satoh
  • Organizer: American Heart Association
  • Place of Presentation: Orlando(アメリカ)
  • Year and Date: 2009-11-15
• [Presentation] Cyclophilin A enhances vascular oxidative stress and the development of angiotensin II-induced aortic aneurysms. Young Investigator Award 最優秀賞 (2009)
  • Author(s): 佐藤公雄
  • Organizer: 日本血管生物医学会・受賞講演
  • Place of Presentation: 東京
  • Year and Date: 2009-10-09
• [Book] 血管と酸化ストレス(Angiotensin Research 8:)(野出孝一編) (2011)
  • Author(s): 佐藤公雄
  • Publisher: 先端医学社
• [Book] 病態把握と治療戦略にバイオマーカーを活かす(エリスロポエチンと酸化ストレス応答性サイクロフィリンA Vascular Medicine) (2010)
  • Author(s): 佐藤公雄雄, 下川宏明
  • Publisher: 先端医学社
• [Book] 実験医学『活性酸素シグナルと酸化ストレス研究最前線』心疾患と酸化ストレス H_2O_2が制御する血管弛緩反応の分子機構 (2009)
  • Author(s): 佐藤公雄、下川宏明
  • Total Pages: 10
  • Publisher: 羊土社
• [Remarks] ホームページ等
  • URL: http://www.cardio.med.tohoku.ac.jp/index.html
• [Remarks]
  • URL: http://www.cardio.med.tohoku.ac.jp/index.html
• [Remarks]
  • URL: http://www.cardio.med.tohoku.ac.jp/index.html