Therapeutic regulation of cellular senescence in aortic aneurysm

• Project/Area Number: 19390335
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General surgery
• Research Institution: Kurume University (2008); Yamaguchi University (2007)
• Principal Investigator: AOKI Hiroki Kurume University, 循環器病研究所, 准教授 (60322244)
• Co-Investigator(Kenkyū-buntansha): YOSHIMURA Koichi 山口大学, 医学部, 講師 (00322248)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000); Fiscal Year 2008: ¥10,920,000 (Direct Cost: ¥8,400,000、Indirect Cost: ¥2,520,000); Fiscal Year 2007: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
• Keywords: 大動脈瘤 / 細胞老化 / 機械的ストレス / 細胞周期 / 薬物治療 / 酸化ストレス

Research Abstract

大動脈瘤は、大動脈壁の慢性炎症により局所的な壁の脆弱化・拡張が進行し、ついには破裂・突然死に至る原因不明の疾患である。ヒト大動脈瘤組織において、組織破壊が活発な部分では老化細胞が出現することが見いだされた。さらに大動脈瘤壁組織中のマクロファージが機械的伸展刺激のセンサーとして働いており、炎症性サイトカイン分泌を介して組織炎症、細胞老化を制御する鍵になっていると考えられた。

Research Products

• [Journal Article] RhoH plays critical roles in Fc ε Rl-dependent signal transduction of mast cells (2009)
  • Author(s): Oda H.
  • Journal Title: J Immunol 182 Pages: 957-962
  • Peer Reviewed
• [Journal Article] Identification of cardiac-specific myosin light chain kinase. (2008)
  • Author(s): Chan JY, Takeda M, Briggs LE, Graham ML, Lu JT, Horikoshi N, Weinberg EO, Aoki H, Sato N, Chien KR, Kasahara H
  • Journal Title: Circ Res 102 Pages: 571-580
  • Peer Reviewed
• [Journal Article] Novel Role of Antioxidant-1 (Atox1) as a Copper-dependent Transcription Factor Involved in Cell Proliferation. (2008)
  • Author(s): Itoh S, Kim HW, Nakagawa O, Ozumi K, Lessner SM, Aoki H, Akram K, McKinney RD, Ushio-Fukai M, Fukai T
  • Journal Title: J Biol Chem 283 Pages: 9157-9167
  • Peer Reviewed
• [Journal Article] Role of NonO-histone interaction in TNFalpha-suppressed prolyl-4-hydroxylase alpha1. (2008)
  • Author(s): Zhang C, Zhang MX, Shen YH, Burks JK, Li XN, LeMaire SA, Yoshimura K, Aoki H, Matsuzaki M, An FS, Engler DA, Matsunami RK, Coselli JS, Zhang Y, Wang XL
  • Journal Title: Biochim Biophys Acta 1783 Pages: 1517-1528
  • Peer Reviewed
• [Journal Article] 大動脈瘤に対する薬物治療 (2008)
  • Author(s): 吉村耕一, 青木浩樹, 古谷彰, 濱野公一, 松崎益徳
  • Journal Title: Heart View 12 Pages: 102-108
• [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: 日本農芸化学会会誌 化学と生物 46 Pages: 180-186
• [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 Pages: 836-842
• [Journal Article] 大動脈瘤の分子病態と研究の可能性 (2008)
  • Author(s): 青木浩樹, 吉村耕一, 松崎益徳
  • Journal Title: 実験医学 26 Pages: 2649-2655
• [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 Pages: 1332-1337
• [Journal Article] Role of NonO-histone interaction in TNFalpha-suppressed prolyl-4-hydroxylase alphal (2008)
  • Author(s): Zhang, C.
  • Journal Title: Biochim Biophys Acta 283 Pages: 157-9167
  • Peer Reviewed
• [Journal Article] Novel Role of Antioxidant-1 (Atox1) as a Copper-dependent Transcription Factor Involved in Cell Proliferation (2008)
  • Author(s): Itoh, S.
  • Journal Title: J Biol Chem 283 Pages: 157-9167
  • Peer Reviewed
• [Journal Article] Identification of cardiac-specific myosin light chain kinase (2008)
  • Author(s): Chan, J. Y.
  • Journal Title: Circ Res 102 Pages: 571-580
  • Peer Reviewed
• [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
  • Journal Title: 医学のあゆみ 226 Pages: 836-842
• [Journal Article] 大動脈瘤の分子病態と研究の可能性 (2008)
  • Author(s): 青木浩樹
  • Journal Title: 実験医学 26 Pages: 2008-2008
• [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
  • Journal Title: 日本農芸化学会会誌化学と生物 46 Pages: 180-186
• [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
  • Journal Title: Heart View 12 Pages: 1332-1337
• [Journal Article] 大動脈瘤に対する薬物治療 (2008)
  • Author(s): 吉村耕一
  • Journal Title: Heart View 12 Pages: 102-108
• [Journal Article] TNF-alpha suppresses prolyl-4-hydroxylase alpha1 expression via the ASK1-JNK-NonO pathway. (2007)
  • Author(s): Zhang C, Zhang MX, Shen YH, Burks JK, Zhang Y, Wang J, LeMaire SA, Yoshimura K, Aoki H, Coselli JS, Wang XL
  • Journal Title: Arterioscler Thromb Vasc Biol 27 Pages: 1760-1767
  • Peer Reviewed
• [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 Pages: 1077-1088
  • Peer Reviewed
• [Journal Article] 大動脈瘤の薬物治療:分子病態の多面的制御 (2007)
  • Author(s): 青木浩樹, 吉村耕一, 松崎益徳
  • Journal Title: 分子心血管病 8(1) Pages: 39-45
• [Journal Article] 大動脈瘤の分子標的治療:JNKによる細胞外マトリクス代謝制御 (2007)
  • Author(s): 青木浩樹, 吉村耕一, 松崎益徳
  • Journal Title: Annual Review 循環器2007 Pages: 86-93
• [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 Pages: 43-49
• [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] JNK抑制による大動脈瘤薬物治療の開発 (2007)
  • Author(s): 吉村耕一, 青木浩樹, 松崎益徳
  • Journal Title: 進歩する心臓研究 Vol.XXVII(1) Pages: 8-11
• [Journal Article] Turning back the clock:regression of abdominal aortic aneurysms via phannacotherapy (2007)
  • Author(s): Aoki, H.
  • Journal Title: J Mol Med 85 Pages: 1077-1088
  • Peer Reviewed
• [Journal Article] TNF-alpha suppresses prolyl-4-hydroxylase alphal expression via the ASK1-JNK-NonO pathway (2007)
  • Author(s): Zhang, C.
  • Journal Title: Arterioscler Thromb Vasc Biol 27 Pages: 1760-1767
  • Peer Reviewed
• [Journal Article] 大動脈瘤の分子標的治療:JNKによる細胞外マトリクス代謝制御 (2007)
  • Author(s): 青木 浩樹
  • Journal Title: Annual Review循環器2007 Pages: 86-93
• [Journal Article] 大動脈瘤の薬物治療 (2007)
  • Author(s): 青木 浩樹
  • Journal Title: Angiology Frontier 6 Pages: 43-49
• [Presentation] Tenascin-C is Tissue Protective during the Development of Abdominal Aortic Aneurysm in Mice (2009)
  • Author(s): Taizo Kimura
  • Organizer: 第73回日本循環器学会
  • Place of Presentation: 大阪
  • Year and Date: 2009-03-22
• [Presentation] Stage-Specific Molecular Therapy for Abdominal Aortic Aneurysm (シンポジウム「大動脈疾患の新しい診断と治療」) (2009)
  • Author(s): 青木浩樹
  • Organizer: 第73回日本循環器学会
  • Place of Presentation: 大阪
  • Year and Date: 2009-03-21
• [Presentation] Involvement of JNK2 in Mechanosensing and Proinflammatory Signaling during Development of Aortic Aneurysm. (2009)
  • Author(s): Koichi Yoshimura
  • Organizer: 第73回日本循環器学会
  • Place of Presentation: 大阪
  • Year and Date: 2009-03-21
• [Presentation] Stage-Specific Molecular Therapy for Abdominal Aortic Aneurysm シンポジウム「大動脈疾患の新しい診断と治療」 (2009)
  • Author(s): Hiroki Aoki, Koichi Yoshimura, Hiroshi Shigematsu, Tsutomu Imaizumi, Masunori Matsuzaki
  • Organizer: 第73回日本循環器学会
• [Presentation] Tenascin-C is Tissue Protective during the Development of Abdominal Aortic Aneurysm in Mice (2009)
  • Author(s): Taizo Kimura, Koichi Yoshimura, Hiroki Aoki, Yasuhiro Ikeda, Kyoko Imanaka-yoshida, Michiaki Hiroe, Kazutaka Aonuma, Masunori Matsuzaki
  • Organizer: 第73回日本循環器学会
• [Presentation] Involvement of JNK2 in Mechanosensing and Proinflammatory Signaling during Development of Aortic Aneurysm (2009)
  • Author(s): Koichi Yoshimura, Hiroki Aoki, Taizo Kimura, Yasuhiro Ikeda, Hidekazu Aoyama, Yosuke Miyazaki, Noriyasu Morikage, Akira Furutani, Kimikazu Hamano, Masunori Matsuzaki
  • Organizer: 第73回日本循環器学会
• [Presentation] RhoH Plays Critical Roles in Fc ε RI-dependent Signal Transduction of Mast Cells (2008)
  • Author(s): Oda H.
  • Organizer: The American Society for Cell Biology 48th Annual Meeting (December 13-17, 2008. San Francisco, CA, USA. )
  • Place of Presentation: San Francisco, CA, U.S.A.
  • Year and Date: 2008-12-14
• [Presentation] 大動脈瘤の分子標的治療(ミニシンポジウム「心血管疾患の診断・治療の新戦略」) (2008)
  • Author(s): 青木浩樹
  • Organizer: 第30回心筋生検研究会
  • Place of Presentation: 津
  • Year and Date: 2008-11-28
• [Presentation] 山口大学医学部・第4回准講会セミナー (2008)
  • Author(s): 青木浩樹
  • Organizer: 大動脈瘤の謎と幸運の鍵
  • Place of Presentation: 宇部
  • Year and Date: 2008-11-14
• [Presentation] The Vascular Smooth Muscle Cell-Autonomous Role of Id2 in Phenotypic Modulation In Vitro And Atherogenesis In Vivo (2008)
  • Author(s): Aoki H.
  • Organizer: The American Heart Association Scientific Sessions 2008
  • Place of Presentation: New Orleans, LA, U.S.A.
  • Year and Date: 2008-11-10
• [Presentation] Protective Role of Tenascin-C during The Development of Aortic Aneurysm in Mice (2008)
  • Author(s): Kimura K
  • Organizer: 2008 Stanford AAA Summit : Strategies for Multidisciplinary Research
  • Place of Presentation: Stanford, CA, U.S.A.
  • Year and Date: 2008-09-04
• [Presentation] 分子病態の包括的理解をめざして (2008)
  • Author(s): 青木浩樹(主催)
  • Organizer: 第1回大動脈瘤分子病態研究会
  • Place of Presentation: 久留米
  • Year and Date: 2008-08-28
• [Presentation] オーバービュー〜分子病態の包括的理解をめざして〜 (2008)
  • Author(s): 青木浩樹
  • Organizer: 第1回大動脈瘤分子病態研究会
  • Place of Presentation: 久留米
  • Year and Date: 2008-08-28
• [Presentation] 大動脈瘤の分子病態 (2008)
  • Author(s): 青木浩樹
  • Organizer: 山口県高血圧と脈管研究会
  • Place of Presentation: 宇部
  • Year and Date: 2008-04-25
• [Presentation] 大動脈瘤の分子標的治療 ミニシンポジウム「心血管疾患の診断・治療の新戦略」 (2008)
  • Author(s): 青木浩樹, 吉村耕一, 松崎益徳
  • Organizer: 第30回心筋生検研究会
  • Place of Presentation: 津
• [Presentation] テネイシンCは腹部大動脈瘤の疾患活動部位に発現し、動脈壁を保護する (2008)
  • Author(s): 木村泰三, 吉村耕一, 青木浩樹, 青沼和隆, 松崎益徳
  • Organizer: 第30回心筋生検研究会
  • Place of Presentation: 津
• [Presentation] RhoH Plays Critical Roles in FceRI-dependent Signal Transduction of Mast Cells (2008)
  • Author(s): Oda H, Fujimoto M, Patrick MS, Aoki H, Shirai M, Suzuki H
  • Organizer: The American Society for Cell Biology 48th Annual Meeting
  • Place of Presentation: San Francisco, CA, USA.
• [Presentation] The Vascular Smooth Muscle Cell-Autonomous Role of Id2 in Phenotypic Modulation In Vitro And Atherogenesis In Vivo (2008)
  • Author(s): Aoki H, Yoshimura K, Ikeda Y, Matsuzaki M
  • Organizer: The American Heart Association Scientific Sessions 2008
  • Place of Presentation: . New Orleans, LA, USA
• [Presentation] Protective Role of Tenascin-C during The Development of Aortic Aneurysm in Mice 2008 Stanford AAA Summit : Strategies for Multidisciplinary Research (2008)
  • Author(s): Kimura K, Yoshimura K, Aoki H, Ikeda Y, Imanaka-Yoshida K, Yoshida T, Hiroe M, Aonuma K, Matsuzaki M
  • Place of Presentation: Stanford, CA, USA
• [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] 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] 細胞外マトリクス安定化は、炎症シグナルを阻害し、マウス腹部大動脈瘤進展を抑制する (2007)
  • Author(s): 青木 浩樹
  • Organizer: 第15回日本血管生物医学会学術大会
  • Place of Presentation: 福岡
  • Year and Date: 2007-11-29
• [Presentation] スタチンは、NF-κB阻害を介してヒト腹部大動脈瘤壁の炎症シグナルを抑制する (2007)
  • Author(s): 青木 浩樹
  • Organizer: 第15回日本血管生物医学会学術大会
  • Place of Presentation: 福岡
  • Year and Date: 2007-11-29
• [Presentation] c-Jun N-terminal kinase 1は、小胞体ストレス反応を介してアディポネクチン分解を促進する (2007)
  • Author(s): 青木 浩樹
  • Organizer: 第11回Molecular Cardiovascular Conference
  • Place of Presentation: 北海道余市郡赤井川村
  • Year and Date: 2007-09-14
• [Presentation] 大動脈瘤の分子病態解明と治療への応用 (2007)
  • Author(s): 青木浩樹, 吉村耕一
  • Organizer: TOKYO HEART FORUM
  • Place of Presentation: 京王プラザホテル 東京
  • Year and Date: 2007-07-20
• [Presentation] 大動脈瘤の分子病態解明と治療への応用 (2007)
  • Author(s): 青木 浩樹
  • Organizer: TOKYO HEART FORUM
  • Place of Presentation: 東京
  • Year and Date: 2007-07-20
• [Presentation] 大動脈瘤の分子病態解明と治療への応用 (2007)
  • Author(s): 青木浩樹
  • Organizer: Cardiology Research Conference in Tsukuba
  • Place of Presentation: 筑波大学 筑波
  • Year and Date: 2007-04-19
• [Presentation] 大動脈瘤の分子病態解明と治療への応用 (2007)
  • Author(s): 青木 浩樹
  • Organizer: Cardiology Research Conference in Tsukuba
  • Place of Presentation: 筑波
  • Year and Date: 2007-04-19
• [Presentation] 大動脈瘤の分子病態 (2007)
  • Author(s): 青木浩樹
  • Organizer: 第15回 William Ganz Symposium
  • Place of Presentation: 秋田
  • Year and Date: 2007-04-14
• [Presentation] 大動脈瘤の分子病態 (2007)
  • Author(s): 青木 浩樹
  • Organizer: 第15回William Ganz Symposium
  • Place of Presentation: 秋田
  • Year and Date: 2007-04-14
• [Presentation] 大動脈瘤の分子病態 (2007)
  • Author(s): 青木浩樹
  • Organizer: 第4回 Organ Microcirculation Forum
  • Place of Presentation: 慶應義塾大学 東京
  • Year and Date: 2007-04-13
• [Presentation] JNK Activation Causes Endoplasmic Reticulum Stress Response in Adipocytes to Suppress (2007)
  • Author(s): Aoki H, Itoh S, Matsumoto S, Yoshimura K, Ikeda Y, Matsuzaki M
  • Organizer: The Adiponectin Secretion In Vivo. American Society for Cell Biology 47th Annual Meeting
  • Place of Presentation: Washington DC, USA
• [Presentation] 細胞外マトリクス安定化は、炎症シグナルを阻害しマウス腹部大動脈瘤進展を抑制する (2007)
  • Author(s): 青木浩樹, 吉村耕一, 小野田雅彦, 池田安宏, 古谷 彰, 濱野公一, 松崎益徳
  • Organizer: 第15回日本血管生物医学会学術大会
  • Place of Presentation: 九州大学医学部百年講堂 福岡
• [Presentation] スタチンは、NF-kB阻害を介してヒト腹部大動脈瘤壁の炎症シグナルを抑制する (2007)
  • Author(s): 青木浩樹, 吉村耕一, 森景則保, 池田安宏, 古谷 彰, 濱野公一, 松崎益徳
  • Organizer: 第15回日本血管生物医学会学術大会
  • Place of Presentation: 九州大学医学部百年講堂 福岡
• [Presentation] Combinatorial Effect of Statins and JNK Inhibitor on Proinflammatory Signaling in Human Abdominal Aortic Aneurysm Tissue. (2007)
  • Author(s): Yoshimura K, Aoki H, Onoda M, Ikeda Y, Aoyama H, Morikage N, Furutani A, Hamano K, Matsuzaki M
  • Organizer: American Heart Association Scientific Sessions 2007
  • Place of Presentation: Florida
• [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: Florida
• [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 2007
  • Place of Presentation: Florida
• [Presentation] Regression of Abdominal Aortic Aneurysm through Pharmacologic Therapy. (2007)
  • Author(s): Yoshimura K, Aoki H, Hamano K, Matsuzaki M
  • Organizer: 8th Annual International Symposium on Advances in Understanding Aortic Diseases.
  • Place of Presentation: Tokyo
• [Presentation] c-Jun N-terminal kinase 1は、小胞体ストレス反応を介してアディポネクチン分解を促進する (2007)
  • Author(s): 青木浩樹, 伊東壮平, 松本祥子, 吉村耕一, 池田安宏, 松崎益徳
  • Organizer: 第11回Molecular Cardiovascular Conference
  • Place of Presentation: ホテルピアノ 北海道余市郡赤井川村
• [Presentation] HMG-CoA Reductase Inhibitors reduce Matrix Metalloproteinase-9 Activity in Human Varicose Veins. (2007)
  • Author(s): Nomura S, Yoshimura K, Morikage N, Furutani A, Aoki H, Matsuzaki M, Hamano K
  • Organizer: World Congress of the International Union of Phlebology.
  • Place of Presentation: Kyoto
• [Presentation] JNK Activation Causes Endoplasmic Reticulum Stress Response in Adipocytes to Suppress the Adiponectin Secretion In Vivo (2007)
  • Author(s): Aoki, H.
  • Organizer: American Society for Cell Biology 47th Annual Meeting
  • Place of Presentation: Washington D.C.,U.S.A.
• [Patent(Industrial Property Rights)] 薬物送達システム (2008)
  • Inventor(s): 青木浩樹
  • Industrial Property Rights Holder: 山口大学
  • Acquisition Date: 2008-12-19
  • Overseas
• [Patent(Industrial Property Rights)] 薬物送達システム 特許出願中 (2007)
  • Inventor(s): 青木浩樹, 吉村耕一, 堤宏守, 照山智恵, 松崎益徳, 黒田俊一
  • Industrial Property Number: 2007-331948
  • Filing Date: 2007-12-25
• [Patent(Industrial Property Rights)] 薬物送達システム (2007)
  • Inventor(s): 青木 浩樹
  • Industrial Property Rights Holder: 山口大学
  • Industrial Property Number: 2007-331948
  • Filing Date: 2007-12-25