Pharmacologic therapy for aortic aneurysm by inhibiting inflammasome

• Project/Area Number: 19591483
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General surgery
• Research Institution: Yamaguchi University
• Principal Investigator: YOSHIMURA Koichi Yamaguchi University, 医学部, 講師 (00322248)
• Co-Investigator(Kenkyū-buntansha): AOKI Hiroki 山口大学, 医学部, 特命准教授 (60322244)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 大動脈瘤 / 伸展刺激 / マクロファージ / 炎症 / 薬物治療

Research Abstract

大動脈瘤は破裂死に至る臨床上重要な疾患であるが、発症原因は未だ不明である。本研究では、大動脈瘤壁細胞への異常な伸展刺激と大動脈瘤の中心病態である慢性炎症との関連を検討した。すなわち、マクロファージは、細胞進展刺激に応答して炎症シグナルを活性化し、さらに炎症性サイトカインの分泌を亢進した。また、このマクロファージの刺激応答は、自然免疫における炎症惹起蛋白複合体inflammasomeのエフェクター分子であるCaspase-1の阻害剤で抑制された。

Research Products

• [Journal Article] 大動脈瘤に対する薬物療法のup-to-date (2008)
  • Author(s): 吉村耕一, 青木浩樹, 木村泰三, 古谷彰, 濱野公一, 松崎益徳
  • Journal Title: Heart View 12(11) Pages: 54-59
• [Journal Article] 大動脈瘤に対する薬物療法開発の最前線 (2008)
  • Author(s): 吉村耕一, 青木浩樹, 松崎益徳
  • Journal Title: 医学のあゆみ 226(10) Pages: 7495-7501
• [Journal Article] 大動脈瘤のトランスレーショナルリサーチ (2008)
  • Author(s): 青木浩樹, 吉村耕一, 松崎益徳
  • Journal Title: 化学と生物 46(3) Pages: 180-186
• [Journal Article] Regression of Abdominal Aortic Aneurysms by Pharmacological Inhibition of c-Jun N-terminal Kinase (2007)
  • Author(s): Yoshimura K, Aoki H, Ikeda Y, Furutani A, Hamano K, Matsuzaki M
  • Journal Title: Bull Yamaguchi Med School 54(3-4) Pages: 29-31
  • NAID: 120000860128
  • Peer Reviewed
• [Journal Article] 大動脈瘤の薬物治療 (2007)
  • Author(s): 青木浩樹, 吉村耕一, 松崎益徳
  • Journal Title: Angiology Frontier 6(4) Pages: 43-49
• [Journal Article] Turning back the clock : regression of abdominal aortic aneurysms via pharmacotherapy (2007)
  • Author(s): Aoki H, Yoshimura K, Matsuzaki M
  • Journal Title: J Mol Med 85(10) Pages: 1077-88
  • Peer Reviewed
• [Presentation] Involvement of JNK2 in Mechanosensing and Proinflammatory Signaling during Development of Aortic Aneurysm (2009)
  • Author(s): Yoshimura K, Aoki H, Kimura T, Ikeda Y, Aoyama H, Miyazaki Y, Morikage N, Furutani A, Hamano K, Matsuzaki M.
  • Organizer: 日本循環器学会
  • Place of Presentation: 大阪
• [Presentation] 大動脈瘤トランスレーショナルリサーチの最前線 (2008)
  • Author(s): 吉村耕一
  • Organizer: 第92回日本循環器学会中国・四国合同地方会
  • Place of Presentation: 下関
  • Year and Date: 2008-06-06
• [Presentation] c-Jun N-terminal Kinase 2 Translates Mechanical Stress to Inflammatory Signal in Macrophages and Promotes Progression of Abdominal Aortic Aneurysm In Vivo (2008)
  • Author(s): Yoshimura K, Aoki H, Kimura T, Ikeda Y, Aoyama H, Morikage N, Furutani A, Hamano K, Matsuzaki M
  • Organizer: American Heart Association Scientific Sessions 2008
  • Place of Presentation: New Orleans, LA, U.S.A.
• [Presentation] Pharmacological therapy of AAA in animal (2008)
  • Author(s): Yoshimura K, Aoki H, Ikeda Y, Furutani A, Hamano K, Matsuzaki M
  • Organizer: International Meeting on Aortic Aneurysms -New insights into an old problem-
  • Place of Presentation: Liege, Belgium
• [Presentation] 大動脈瘤の病態解明と薬物療法開発の試み (2008)
  • Author(s): 吉村耕一, 青木浩樹, 池田安宏, 濱野公一, 松崎益徳
  • Organizer: 第56回日本心臓病学会
  • Place of Presentation: 東京
• [Presentation] Critical Role of JNK in Chronic Inflammation of Abdominal Aortic Aneurysms (2008)
  • Author(s): Yoshimura K, Aoki H, Ikeda Y, Hamano K, Matsuzaki M
  • Organizer: 日本循環器学会
  • Place of Presentation: 博多
• [Presentation] Critical Role of JNK2 for Development of Abdominal Aortic Aneurysm in Mice (2008)
  • Author(s): Yoshimura K, Aoki H, Ikeda Y, Morikage N, Furutani A, Hamano K, Matsuzaki M
  • Organizer: 日本循環器学会
  • Place of Presentation: 博多
• [Presentation] cJun N-terminal Kinase 2 Translates Mechanical Stress to Inflammatory Signal in Macrophages and Promotes Progression of Abdominal Aortic Aneurysm In Vivo (2008)
  • Author(s): 吉村耕一, 他
  • Organizer: American Heart Association Scientific Sessions 2008
  • Place of Presentation: 米国ニューオリンズ
• [Presentation] Regression of Abdominal Aortic Aneurysm in animal models (2007)
  • Author(s): Yoshimura K, Aoki H, Ikeda Y, Matsuzaki M
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: Orlando, Florida, U.S.A.
• [Presentation] c-Jun N-terminal Kinase 2 is Required for Development of Abdominal Aortic Aneurysm in Mice (2007)
  • Author(s): Yoshimura K, Aoki H, Ikeda Y, Aoyama H, Morikage N, Furutani A, Hamano K, Matsuzaki M
  • Organizer: American Heart Association Scientific Sessions 2007
  • Place of Presentation: Orlando, Florida, U.S.A.
• [Presentation] Regression of Abdominal Aortic Aneurysm through Pharmacologic Therapy. 8th annual international (2007)
  • Author(s): Yoshimura K, Aoki H, Hamano K, Matsuzaki M.
  • Organizer: symposium on advances in understanding aortic diseases
  • Place of Presentation: Tokyo
• [Book] Edition de I'Universite de Liege, Liege (2008)
  • Author(s): Yoshimura K, Aoki H, Ikeda Y, Furutani A, Hamano K, Matsuzaki M
  • Publisher: In the Text Book"Aortic Aneurysms, New insights into an old problem" (ed. by Sakalihasan N.)