New Mechanisms of the Protection against the Increase in Oxidative Stress in Hypertension

• Project/Area Number: 21590954
• 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: Yamaguchi University
• Principal Investigator: UMEMOTO Seiji 山口大学, 医学部附属病院, 准教授 (90263772)
• Co-Investigator(Kenkyū-buntansha): YOSHIMURA Kohichi 山口大学, 大学院・医学系研究科, 准教授 (00322248)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: Oxidative stress / Toll-like receptor / Angiotensin II / Superoxide dismutase / hypertension / oxidative stress / superoxide dismutase / Toll-like reveptor

Research Abstract

Angiotensin II(AngII) increased oxidative stress and induced vascular remodeling through AngII type 1 receptor via TLR4, whereas TLR4 directly inhibited ecSOD to promote the production of oxidative stress and vascular remodeling. PPARγwas not involved in these processes.

Research Products

• [Journal Article] Nifedipine activates PPARgamma and exerts antioxidative action through Cu/ ZnSOD independent of blood-pressure lowering in SHRSP (2010)
  • Author(s): Hashimoto R, Umemoto S, Guo F, Umeji K, Itoh S, Kishi H, Kobayashi S, Matsuzaki M
  • Journal Title: J Atheroscler Thromb. 2010 Aug 31 Volume: 17(8) Pages: 785-95
  • Peer Reviewed
• [Journal Article] Nifedipine activates PPARγ and exerts an antioxidative action through Cu/ZnSOD independent of blood-pressure lowering in SHRSP (2010)
  • Author(s): Ryo Hashimoto
  • Journal Title: Journal of Atherosclerosis and Thrombosis Volume: 17 Pages: 785-795
  • Peer Reviewed
• [Presentation] Angiotensin IT Upregulates Oxidative Stress through Toll-like Receptor 4 by Inhibiting ecSOD and ATP7A (2012)
  • Author(s): Nakashima T, Umemoto S, Yoshimura K, Matsuda S, Fukai T, Matsuzaki M
  • Organizer: 第76回日本循環器学会総会・学術集会
  • Place of Presentation: 福岡国際会議場他,福岡
• [Presentation] AngIIはToll-like receptorを介して炎症を惹起し糸球体硬化を促進する (2011)
  • Author(s): 岡本匡史, 作村俊浩, 池上直慶, 中島忠亮, 松田晋, 梅本誠治, 松崎益徳
  • Organizer: 第99回日本循環器学会中国地方会
  • Place of Presentation: 海峡メッセ下関,下関
  • Year and Date: 2011-11-26
• [Presentation] Toll-like Receptor 4 signal adaptor protein MyD88はアンジオテンシンIIによるNADPH oxidase活性化と血管リモデリングに関与する (2011)
  • Author(s): 岡本匡史, 梅本誠治, 中島忠亮, 松田晋, 松崎益徳
  • Organizer: 第3回腎疾患と高血圧研究会
  • Place of Presentation: ホテルエルセラーン大阪,大阪
  • Year and Date: 2011-07-02
• [Presentation] Toll-like receptorsignal adaptor protein MyD88 regulatesNAD(P) H oxidase-generated oxidative stress and vascular remodeling in angiotensin II-induced hypertension (2011)
  • Author(s): Nakashima T, Umemoto S, Matsuda S, Okamoto T, Murata T, Yoshimura K, FukaiT, Matsuzaki M
  • Organizer: ESC Congress 2011
  • Place of Presentation: Paris, France
• [Presentation] Toll-like receptor signal adaptor protein MyD88 regulates NAD(P)H oxidase-generated oxidative stress and vascular remodeling in angiotensin II-induced hypertension (2011)
  • Author(s): Nakashima T, Umemoto S, Matsuda S, Okamoto T, Murata T, Yoshimura K, Fukai T, Matsuzaki M
  • Organizer: ESC Congress 2011
  • Place of Presentation: Paris, France
• [Presentation] Angiotensin II Upregulates Oxidative Stress through Toll-like Eeceptor 4 by Inhibiting ecSOD and ATP7A (2011)
  • Author(s): Nakashima T, Umemoto S, Matsuda S, Okamoto T, Murata T, Yoshimura K, Fukai T, Matsuzaki M
  • Organizer: 第75回日本循環器学会総会・学術集会
  • Place of Presentation: パシフィコ横浜,横浜
• [Presentation] MyD88はアンジオテンシンITによりNADPH oxidaseを制御することで血管リモデリングを引き起こす重要な役割を果たす (2011)
  • Author(s): 中島忠亮, 梅本誠治, 岡本匡史, 松田晋, 松崎益徳
  • Organizer: 第34回日本高血圧学会総会
  • Place of Presentation: 栃木県総合文化センター,宇都宮
• [Presentation] Toll-like receptor signal adaptor protein MyD88 is important in regulating NADPH oxidase-generated oxidative stress and vascular remodeling (2011)
  • Author(s): Nakashima T, Umemoto S, Matsuda S, Okamoto T, Murata T, Yoshimura K, Fukai T, Matsuzaki M
  • Organizer: 第43回日本動脈硬化学会総会・学術集会
  • Place of Presentation: ロイトン札幌,札幌
• [Presentation] AgnIIはTLR4を介して酸化ストレスを増加させ糸球体硬化を惹起する (2010)
  • Author(s): 岡本匡史
  • Organizer: 第97回日本循環器学会中国地方会
  • Place of Presentation: 島根県松江市くにびきメッセ
  • Year and Date: 2010-12-04
• [Presentation] Toll-like receptor 4 selectively activates MCP-1to induce cardiac hypertrophy and dysfunction in angiotensin II-inducedhypertension (2010)
  • Author(s): Matsuda S, Umemoto S, Yoshino H, Nakashima T, Ito S, Aoki H, YoshimuraK, Murata T, Matsuzaki M
  • Organizer: ESC Congress 2010
  • Place of Presentation: Stockholm, Sweden
• [Presentation] Toll-like receptor 4 selectively activates MCP-1 to induce cardiac hypertrophy and dysfunction in angiotensin II-induced hypertension (2010)
  • Author(s): Susumu Matsuda
  • Organizer: ESC Congress 2010
  • Place of Presentation: Stockholm, Sweden
• [Presentation] Toll-like receptor 4 selectively activates MCP-1 to induce cardiac hypertrophy and dysfunction in angiotensin II-induced hypertension (2010)
  • Author(s): Susumu Matsuda
  • Organizer: 第42回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 岐阜県岐阜市長良川国際会議場
• [Presentation] Toll-like Receptor 4 regulates MCP-1 independently of NAD(P)H oxidase-mediated ROS production (2010)
  • Author(s): Hiroko Yoshino
  • Organizer: 第74回日本循環器学会総会・学術集会
  • Place of Presentation: 京都国際会議場,京都
• [Presentation] TLR4 activates JNK2 and MCP-1 to induce cardiac hypertrophy and dysfunction in ATII-induced hypertension (2010)
  • Author(s): Susumu Matsuda
  • Organizer: 第74回日本循環器学会総会・学術集会
  • Place of Presentation: 京都国際会議場,京都
• [Presentation] アンジオテンシンIIはTLR4を介する心筋内酸化ストレス増加により心機能低下させる (2009)
  • Author(s): 松田晋
  • Organizer: 第95回日本循環囂学会中国・四国地方会
  • Place of Presentation: ホテルオークラ岡山,岡山
  • Year and Date: 2009-11-28
• [Presentation] Toll-like receptor 4 increases oxidative stress by inhibiting the upregulation of extracellular superoxide dismutase in angiotensin II-induced hypertension (2009)
  • Author(s): Yoshino H, Umemoto S, Matsuda S, Nakashima T, Itoh S, Aoki H, YoshimuraK, Murata T, Fukai T, Matsuzaki M
  • Organizer: ESC Congress2009
  • Place of Presentation: Barcelona, Spain
• [Presentation] Angiotensin II induces cardiac systolic and diastolic dysfunction via Toll-like receptor 4 mediated upregulation of oxidative stress in murine heart (2009)
  • Author(s): Matsuda S, Umemoto S, Yoshino H, AokiH, Itoh S, Yoshimura K, Murata T, Matsuzaki M
  • Organizer: The American Society of Hypertension, Inc 24^<rd> Annual Scientific Meeting and Exposition
  • Place of Presentation: San Francisco, USA
• [Presentation] Toll-like receptor 4 augments angiotensin II-inducedoxidative stress by inhibiting the upregulation of extracellular superoxide dismutase (2009)
  • Author(s): Yoshino H, Umemoto S, Matsuda S, ItohS, Aoki H, Yoshimura K, Murata T, FukaiT, Matsuzaki M
  • Organizer: The American Society of Hypertension, Inc 24^<rd> Annual Scientific Meeting and Exposition
  • Place of Presentation: San Francisco, USA
• [Presentation] Toll-like receptor 4 increases oxidative stress by inhibiting the upregulation of extracellular superoxide dismutase in angiotensin 11-induced hypertension (2009)
  • Author(s): Hiroko Yoshino
  • Organizer: ESC Congress 2009
  • Place of Presentation: Fira Gran Via, Barcelona, Spain
• [Presentation] Jun-terminal kinase2 is involved in angiotensin II-induced oxidative stress and cardiac dysfunction via Toll-like receptor 4 (2009)
  • Author(s): Susumu Matsuda
  • Organizer: ESC Congress 2009
  • Place of Presentation: Fira Gran Via, Barcelona, Spain
• [Presentation] Toll-like receptor 4 augments angiotensin II-induced oxidative stress by inhibiting the upregulation of extracellular superoxide dismutase (2009)
  • Author(s): Hiroko Yoshino
  • Organizer: 10th International symposium on mechanisms of vasodilatation
  • Place of Presentation: ホテル大観荘,宮城
• [Presentation] Toll-like receptor 4 augments angiotensin II-induced oxidative stress by inhibiting the upregulation of extracellular superoxide dismutase (2009)
  • Author(s): Hiroko Yoshino
  • Organizer: The American Society of Hypertension, Inc 24rd Annual Scientific Meeting and Exposition
  • Place of Presentation: the San Francisco Marriott, San Francisco, U.S.A
• [Presentation] Angiotensin II induces cardiac systolic and diastolic dysfunction via Toll-like receptor 4 mediated upregulation of oxidative stress in murine heart (2009)
  • Author(s): Susumu Matsuda
  • Organizer: The American Society of Hypertension, Inc 24rd Annual Scientific Meeting and Exposition
  • Place of Presentation: the San Francisco Marriott, San Francisco,U.S.A
• [Presentation] Angiotensin IIはToll-like receptor4を介してJunNH2-terminal kinase2活性化と心筋内酸化ストレス増加を惹起して心機能低下させる (2009)
  • Author(s): 松田晋
  • Organizer: 第32回日本高血圧学会総会
  • Place of Presentation: 大津プリンスホテル,滋賀
• [Presentation] Nidedipine activates PPARγ beyond blood-pressure lowering and exerts an antiatherogenic antioxidant action through Cu/ZnSOD in SHRSP (2009)
  • Author(s): Ryo Hashimoto
  • Organizer: 第41回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 海峡メッセ,山口
• [Presentation] Angiotensin II induces cardiac systolic and diastolic dysfunction via Toll-like receptor 4 mediated upregulation of oxidative stress in murine heart (2009)
  • Author(s): Susumu Matsuda
  • Organizer: 第41回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 海峡メッセ,山口
• [Presentation] Toll-like receptor 4 increases oxidative stress by inhibiting the upregulation of extracellular superoxide dismutase in Angiotensin II-induced hypertension (2009)
  • Author(s): Hiroko Yoshino
  • Organizer: 第41回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 海峡メッセ,山口
• [Presentation] Antioxidant 1 : a novel copper dependent transcription factor for extracellular superoxide dismutase (2009)
  • Author(s): Shinichi Ito
  • Organizer: 第41回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 海峡メッセ,山口
• [Presentation] Angiotensin II負荷においてTLR4はecSODを抑制し酸化ストレスを増加させる (2009)
  • Author(s): 吉野敬子
  • Organizer: 第94回日本循環器学会中国・四国地方会
  • Place of Presentation: 高知かるぽ一と,高知
• [Remarks]
  • URL: http://ds.cc.yamaguchi-u.ac.jp/.ninai/
• [Remarks]
  • URL: http://ds.cc.yamaguchi-u.ac.jp/~ninai/