A novel therapeutic strategy for glucocorticoid-induced vascula endothelial dysfundtion

• Project/Area Number: 19590866
• 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: The University of Tokushima
• Principal Investigator: AKAIKE Masashi The University of Tokushima, 大学院・ヘルスバイオサイエンス研究部, 准教授 (90271080)
• Co-Investigator(Kenkyū-buntansha): AIHARA Ken-ihchi 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 講師 (70372711) ; IWASE Takashi 徳島大学, 医学部・歯学部附属病院, 助教 (10403718)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 血管内皮機能 / 酸化ストレス / 活性酸素 / 一酸化窒素 / 一酸化窒素合成酵素 / グルココルチコイド / スタチン / ERK5 / KLF2 / HMGCoA還元酵素阻害薬 / 血管内皮細胞 / 高血圧 / 多面的作用 / ゲラニルゲラニルピリン酸

Research Abstract

グルココルチコイド過剰マウスでは, 血圧上昇、血管内皮機能低下, 酸化ストレス増加、一酸化窒素産生低下がみられ, これらはピタバスタチンにより改善した. 培養ヒト臍帯静脈血管内皮細胞では, ピタバスタチンはデキサメサゾンによる活性酸素産生の増加と内皮型一酸化窒素合成酵素の発現低下を改善し、この作用はイソプレノイド中間体であるゲラニルゲラニルピロリン酸により完全に消失した. ピタバスタチンは血管内皮細胞に対する多面的作用により, グルココルチコイド誘発性血管障害の新規治療法となる可能性がある.

Research Products

• [Journal Article] ステロイド投与下におけるスタチンと血管内皮 (2009)
  • Author(s): 赤池雅史, 松本俊夫
  • Journal Title: 災害外科 (in press)
• [Journal Article] Heparin cofactor II, a novel vascular remodeling factor : its clinical significance and molecular pathogenesis in atherosclerosis (2009)
  • Author(s): Aihara K, Azuma H, Akaike M, Sata M, Matsumoto T
  • Journal Title: J Atheroscier Thromb (in press)
  • Peer Reviewed
• [Journal Article] Heparin Cofactor II Is an Independent Protective Factor Against Peripheral Arterial Disease in Elderly Subjects With Gardiovascular Risk Factors (2009)
  • Author(s): Aihara K, Azuma H, Akaike M, Kurobe H, Sumitomo Y, Yoshida S, Ise T, Iwase T, Ishikawa K, Sata M, Kitagawa T, Matsumoto T
  • Journal Title: J Atherascler Thramb (in press)
  • Peer Reviewed
• [Journal Article] Androgen-Androgen Receptor System Protects against Angiotensin II-Induced Vascular Remodeling (2009)
  • Author(s): Ikeda Y, Aihara K, Yoshida S, Sato T, Yagi S, Iwase T, Sumitomo Y, Ise T, Ishikawa K, Azuma H, Akaike M, Kato S, Matsumoto T
  • Journal Title: Endcrinology 150(6) Pages: 2857-2864
  • Peer Reviewed
• [Journal Article] Infective endocarditis caused by lactobacillus (2008)
  • Author(s): Yagi S, Akaike M, Fujimura M, Ise T, Yoshida S, Sumitomo Y, Ikeda Y, Iwase T, Aihara K, Azuma H, Kurushima A, Ichikawa Y, Kitagawa T, Kimura T, Nishiuchi T, Matsumoto T
  • Journal Title: Intern Med 47(12) Pages: 1113-6
  • NAID: 130000078859
  • Peer Reviewed
• [Journal Article] Impact of serum insulin-like growth factor-1 on early prognosis in acute myocardial infarction (2008)
  • Author(s): Yamaguchi H, Komamura K, Choraku M, Hirono A, Takamori N, Tamura K, Akaike M, Azuma H
  • Journal Title: Intern Med 47(9) Pages: 819-25
  • NAID: 130000080011
  • Peer Reviewed
• [Journal Article] Pitavastatin, an HMG-CoA Reductase Inhibitor, Exertse NOS-independent Protective Actions against Angiotensin II-Induced Cardiovascular Remodeling and Renal Insufficiency (2008)
  • Author(s): Yagi S, Aihara K, Ikeda Y, Sumitomo Y, Yoshida S, Ise T, Iwase T, Ishikawa K, Azuma H, Akaike M, Matsumoto T
  • Journal Title: Circ Res 102(1) Pages: 68-76
  • Peer Reviewed
• [Journal Article] Impact of serum insulin-like growth factor-1 on early prognosis in acute myocardial infarction. (2008)
  • Author(s): 赤池 雅史
  • Journal Title: Intern Med 47 Pages: 819-825
  • NAID: 130000080011
  • Peer Reviewed
• [Journal Article] 高コレステロール血症患者に対するピタバスタチンの有効性-総合的脂質プロファイルに関する検討- (2008)
  • Author(s): 赤池 雅史
  • Journal Title: Pros Med 28 Pages: 2745-2751
  • Peer Reviewed
• [Journal Article] Pitavastatin,an HMG-CoA Reductase Inhibitor,Exerts eNOS-Independent Protective Actions Against Angiotensin II Induced Cardiovascular Remodeling and Renal Insufficiency. (2008)
  • Author(s): 八木 秀介
  • Journal Title: Circ Res 102 Pages: 68-76
  • Peer Reviewed
• [Journal Article] Strain-dependent embryonic lethality and exaggerated vascular remodeling in heparin cofactor II-deficient mice (2007)
  • Author(s): Aihara K, Azuma H, Akaike M, Ikeda Y, Sata M, Takamori N, Yagi S, Iwase T, Sumitomo Y, Sato T, Nakamichi Y, Yamamoto Y, Yoshimora K, Watanabe T, Nakamura T, Oomizu A, Tsukada M, Hayashi H, Sudo T, Kato S, Matsumoto T
  • Journal Title: J Clin Invest 117 Pages: 1486-9
  • Peer Reviewed
• [Journal Article] ステロイド過剰によるNO bioavailabilityの低下と血管内皮機能障害 (2007)
  • Author(s): 赤池雅史, 松本俊夫
  • Journal Title: CLINICAL CALCIUM 17(6) Pages: 864-870
• [Journal Article] Strain-dependent embryonic lethality and exaggerated vadcular remodeling in heparin cofactor II-deficient mice. (2007)
  • Author(s): 粟飯原 賢一
  • Journal Title: J Clin Invest 117 Pages: 1514-1526
  • Peer Reviewed
• [Journal Article] ステロイド過剰によるNO bioavailabilityの低下と血管内皮機能障害 (2007)
  • Author(s): 赤池 雅史
  • Journal Title: CLINICAL CALCIUM 17 Pages: 864-870
  • Peer Reviewed
• [Presentation] Pitavastatin excretese NOS-independent protective action against angiotensin II-induced atrial remodeling through attenuating Rac1-mediated oxidative stress 73^<th> Annual Scientific Meeting of the Japanese (2009)
  • Author(s): Yagi S, Akaiice M, Aihara K, Ishikawa K, Ise T, Yoshida S, Sumitomo Y, Ikeda Y, Iwase T, Soeki T, Matsumoto T, Sata M
  • Organizer: Circulation Society
  • Place of Presentation: Osaka
• [Presentation] Novel eNOS-independent protective action of statin against angiotensinII-induced atrial remodeling via attenuating Racl-mediated oxidative stress (2008)
  • Author(s): 八木 秀介
  • Organizer: American Heart Association Scientific Sessions 2008
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2008-11-10
• [Presentation] Glucocorticoid-induced Hypertension through Increased Nitric Oxide Production as a Pleiotropic Effect on Vascular Endothelial Cells (2008)
  • Author(s): 赤池 雅史
  • Organizer: 22nd Scientific Meeting of the International Society of Hypertension
  • Place of Presentation: Berlin, Germany
  • Year and Date: 2008-06-14
• [Presentation] HMG-CoA Reductase Inhibitor Pitavastatin Increases the Expression of Enothelial NOS through Activation of ERK5-KLF2 Pathway in Vascular Endothelial Cells (2008)
  • Author(s): 赤池 雅史
  • Organizer: 第72回日本循環器学会学術集会
  • Place of Presentation: 福岡市
  • Year and Date: 2008-03-28
• [Presentation] Anovele NOS-independent protective action of statin against angiotensin II-inducedatrial remodeling via attenuating Rac-1-mediaked oxidative stress (2008)
  • Author(s): Yagi S, Akaike M, Aihara K, Ishikawa K, Ise T, Yoshida S, Sumitomo Y, Ikeda Y, Iwase T, Soeki T, Matsumoto T, Sata M
  • Organizer: American Heart Association 2008
  • Place of Presentation: New Orleans, America
• [Presentation] ピタバスタチンはERK5-KLF2経路の活性化を介して血管内皮細胞での一酸化窒素合成酵素の発現を亢進する (2008)
  • Author(s): 赤池雅史, 八木秀介, 粟飯原賢一, 石川カズ江, 池田康将, 吉田守美子, 住友由佳, 岩瀬俊, 阿部純一, 松本俊夫, 佐田政隆
  • Organizer: 第31回日本高血圧学会総会
  • Place of Presentation: 札幌市
• [Presentation] Pitavastatin, an HMG-CoA Rednctase Inhibitor, Prevents Glucocorticaid-induced Hypertension through Increased Nitric Oxide Production as a Pleiotropic Effect on Vascular Endothelial Cells (2008)
  • Author(s): Akaike M, Aihara K, Yagi S, Ikeda Y, Ichikawa K, Ise T, Yoshida S, Sumitomo Y, Iwase T, Matsumoto T
  • Organizer: 22nd Scienkific Meeting of the International Society of Hypertension Berlin
  • Place of Presentation: Germany
• [Presentation] HMG-CoA Reductase Inhibitor Pitavastatin Increases the Expression of Endothelial NOS through Activation of EIZK5-KLF2 Pathway in Vascular Endothelial Cells (2008)
  • Author(s): Akaike M, Yagi S, Aihara K, Ikeda Y, Ishikawa K, Ise T, Yoshida S, Sumitpmo Y, Iwase T, Abe J, Matsumoto T
  • Organizer: 72^<th> Annual Scientific Meething of the Japanese Circulation Society
  • Place of Presentation: Fukuoka
• [Presentation] グルココルチコイド誘発性高血圧に対するピタバスタチンの効果とその機序の検討 (2007)
  • Author(s): 赤池 雅史
  • Organizer: 第30回日本高血圧学会総会
  • Place of Presentation: 宜野湾市
  • Year and Date: 2007-10-25
• [Presentation] 「大腿骨頭壊死症の病態解明」ステロイド性骨壊死と血管内皮障害 (2007)
  • Author(s): 赤池雅史シンポジウム
  • Organizer: 第34回日本股関節学会
  • Place of Presentation: 金沢市
  • Year and Date: 2007-10-11
• [Presentation] ステロイド性骨壊死と血管内皮障害 (2007)
  • Author(s): 赤池 雅史
  • Organizer: 第34回日本股関節学会
  • Place of Presentation: 金沢市
  • Year and Date: 2007-10-11
• [Presentation] グルココルチコイド誘発性高血圧に対するピタバスタチンの効果とその機序の検討 (2007)
  • Author(s): 赤池雅史, 粟飯原賢一, 八木秀介, 池田康将, 石川カズ江、住友由佳, 岩瀬俊, 松本竣夫
  • Organizer: 第30回日本高血圧学会学総会
  • Place of Presentation: 宜野湾市