Role of Inflammasomes as an initial sensor for cardiovascular stress

• Project/Area Number: 20200077
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research a proposed research project)
• Allocation Type: Single-year Grants
• Research Field: Circulatory organs internal medicine; Experimental pathology
• Research Institution: Shinshu University
• Principal Investigator: TAKAHASHI Masafumi Shinshu University, 医学部, 教授 (40296108)
• Co-Investigator(Renkei-kenkyūsha): TANIGUCHI Shun'ichiro (60117166) ; IKEDA Uichi (30221063)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥30,550,000 (Direct Cost: ¥23,500,000、Indirect Cost: ¥7,050,000); Fiscal Year 2010: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000); Fiscal Year 2009: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000); Fiscal Year 2008: ¥12,090,000 (Direct Cost: ¥9,300,000、Indirect Cost: ¥2,790,000)
• Keywords: インフラマソーム / 心血管 / シグナル伝達 / 炎症 / マクロファージ / 心臓 / 虚血再灌流 / 骨髄細胞 / 動脈硬化 / 虚血性心疾患 / 炎症反応

Research Abstract

Inflammation plays a key role in the pathophysiology of cardiovascular diseases. In particular, recent studies suggest that a sterile inflammatory response is mediated through a multiple-protein complex called the inflammasomes. The purpose of this study is to investigate the role of inflammasomes in the pathogenesis of cardiovascular diseases and explore a therapeutic potential of regulating inflammasomes for cardiovascular diseases using a murine model of myocardial ischemia-reperfusion (I/R) injury. Our results demonstrate the importance of inflammasomes for the initial inflammatory response after myocardial I/R and suggest that the inflammasome is a potential novel therapeutic target for preventing myocardial I/R injury.

Research Products

• [Journal Article] Inflammasome activation of cardiac fibroblasts is essential for myocardial ischemia reperfusion injury. (2011)
  • Author(s): Kawaguchi M, Takahashi M, Hata T, Kashima Y, Usui F, Morimoto, Izawa A, Takahashi Y, Masumoto J, Koyama J, Hongo M, Noda T, Nakayama J, Sagara J, Taniguchi S, Ikeda U.
  • Journal Title: Circulation 123 Pages: 594-604
• [Journal Article] Critical role of Th17 cells in inflammation and neovascularization after ischemia. (2011)
  • Author(s): Hata T, Takahashi M, Hida S, Kawaguchi M, Kashima Y, Usui F, Morimoto, Nishiyama A, Izawa A, Koyama J, Iwakura Y, Taki S, Ikeda U.
  • Journal Title: Cardiovasc Res 90 Pages: 364-372
• [Journal Article] Inflammasome activation of cardiac fibroblasts is essential for myocardial ischemia reperfusion injury. (2011)
  • Author(s): Kawaguchi M, Takahashi M, Hata T, Kashima Y, Usui F, Morimoto H, Izawa A, Takahashi Y, Masumoto J, Koyama J, Hongo M, Noda T, Nakayama J, Sagara J, Taniguchi S, Ikeda U.
  • Journal Title: Circulation Volume: 123 Pages: 594-604
  • Peer Reviewed
• [Journal Article] Critical role of Th17 cells in inflammation and neovascularization after ischemia. (2011)
  • Author(s): Hata T, Takahashi M, Hida S, Kawaguchi M, Kashima Y, Usui F, Morimoto H, Nishiyama A, Izawa A, Koyama J, Iwakura Y, Taki S, Ikeda U.
  • Journal Title: Cardiovasc Res Volume: Jan11(in press)
  • Peer Reviewed
• [Journal Article] Role of the SDF-1/CXCR4 system in myocardial infarction. (2010)
  • Author(s): Takahashi M.
  • Journal Title: Circ J 74 Pages: 418-423
  • NAID: 10025943035
• [Journal Article] Immature erythroid cells : a new source for therapeutic angiogenesis (2010)
  • Author(s): Takahashi M.
  • Journal Title: J Mol Cell Cardiol 49 Pages: 341-342
• [Journal Article] Immature erythroid cells : a new source for therapeutic angiogenesis? (2010)
  • Author(s): Takahashi M.
  • Journal Title: J Mol Cell Cardiol Volume: 49 Pages: 341-342
  • Peer Reviewed
• [Journal Article] Role of the SDF-1/CXCR4 system in myocardial infarction. (2010)
  • Author(s): Takahashi M.
  • Journal Title: Circ J Volume: 74 Pages: 418-423
  • NAID: 10025943035
  • Peer Reviewed
• [Journal Article] Therapeutic neovascularization by the implantation of autologous mononuclear cells in patients with connective tissue diseases. (2009)
  • Author(s): Takahashi M, Izawa A, Ishigatsubo Y, Fujimoto K, Miyamoto M, Horie T, Aizawa Y, Amano J, Minota S, Murohara T, Matsubara H, Ikeda U.
  • Journal Title: Curr Pharm Design 15 Pages: 2778-2783
• [Journal Article] Bone marrow CXCR4 induction by cultivation enhances therapeutic angiogenesis. (2009)
  • Author(s): Shiba Y, Takahashi M, Hata T, Murayama H, Morimoto H, Ise H, Nagasawa T, Ikeda U.
  • Journal Title: Cardiovasc Res 81 Pages: 169-177
• [Journal Article] Surface coating of bone marrow cells with N-acetylglucosamine for bone marrow implantation therapy. (2009)
  • Author(s): Kobayashi S, Ise H, Takahashi M, Goto M, Akaike T, Ikeda U.
  • Journal Title: Biomaterials 30 Pages: 574-582
• [Journal Article] Genetic susceptibility to restenosis : Role of bone marrow cells and inflammatory response. (2009)
  • Author(s): Takahashi M.
  • Journal Title: Arterioscler Thromb Vasc Biol 10 Pages: 1407-1408
• [Journal Article] Bone marrow CXCR4 induction by cultivation enhances therapeutic angiogenesis. (2009)
  • Author(s): Shiba, Y., Takahashi, M., Hata, T., Mutrayama, H., Morimoro, H., Ise, H., Nagasawa, T., Ikeda, U.
  • Journal Title: Cardiovasc Res 81(1) Pages: 169-177
  • Peer Reviewed
• [Journal Article] Therapeutic neovascularization by the implantation of autologous mononuclear cells in patients with connective tissue diseases. (2009)
  • Author(s): Takahashi, M., Izawa, A., Ishigatsubo, Y., Fujimoto, K., Miyamoto, M., Horie, T., Aizawa, Y., Amano, J., Minota, S., Murohara, T., Matsubara, H., Ikeda, U.
  • Journal Title: Current Pharmaceutical Design 15(24) Pages: 2778-2783
  • Peer Reviewed
• [Journal Article] Surface coating of bone marrow cells with N-acetylglucosamine for bone marrow implantation therapy. (2009)
  • Author(s): Kobayashi, S., Ise, H., Takahashi, M., Goto, M., Akaike, T., Ikeda, U.
  • Journal Title: Biomaterials 30(4) Pages: 574-582
  • Peer Reviewed
• [Journal Article] Effects of hormone-sensitive lipase disruption on cardiac energy metabolism in reponse to fasting and refeeding. (2009)
  • Author(s): Suzuki,J., Ueno,M., Uno,M., Hirose,Y., Zenimaru,Y., Takahashi,S., Osuga,J., Ishibashi,S., Takahashi,M., Hirose,M., Yamada,M., Kraemer,F,B., Mitamori,I.
  • Journal Title: Am J Physiol Endocrinol Metab 297
  • Peer Reviewed
• [Journal Article] Critical role of bone marrow apoptosis-associated speck-like protein, an inflammasome adaptor molecule, in neointimal formation after vascular injury in mice. (2008)
  • Author(s): Yajima N, Takahashi M, Morimoto H, Shiba Y, Takahashi Y, Masumoto J, Ise H, J Sagara, Nakayama J, Taniguchi S, Ikeda U.
  • Journal Title: Circulation 117 Pages: 3079-3087
• [Journal Article] Deficiency of tumor necrosis factor-alpha and interferon-gamma in bone marrow cells synergistically inhibits neointimal formation following vascular injury. (2008)
  • Author(s): Murayama H, Takahashi M, Takamoto M, Shiba Y, Ise H, Koyama J, Tagawa Y, Iwakura Y, Ikeda U.
  • Journal Title: Cardiovasc Res 80 Pages: 175-180
• [Journal Article] MCP-1 induces cardioprotection against ischemia/reperfusion injury : Role of reactive oxygen species. (2008)
  • Author(s): Morimoto H, Hirose M, Takahashi M, Kawaguchi M, Ise H, Kolattukudy PE, Yamada M, Ikeda U.
  • Journal Title: Cardiovasc Res 78 Pages: 554-562
• [Journal Article] Critical role of bone marrow-derived ASC, an inflammasome adaptor molecule, in neointimal formation after vascular injury in mice (2008)
  • Author(s): Yajima N, Takahashi M, Morimoto H, Shiba Y, Takahashi Y, Masumoto J, Ise H, J Sagara, Nakayama J, Taniguchi S, Ikeda U.
  • Journal Title: Circulation 117 Pages: 3079-3087
  • Peer Reviewed
• [Journal Article] MCP-1 induces cardioprotection against ischemia/reperfusion in jury : Role of reactive oxygen species (2008)
  • Author(s): Morimoto H, Hirose M, Takahashi M, Kawaguchi M, Ise H, Kolattukudy PE, Yamada M, Ikeda U.
  • Journal Title: Cardiovasc Res 78 Pages: 554-562
  • Peer Reviewed
• [Journal Article] High-mobility group box 1 protein (HMBG1) in ischemic heart disease : beneficial or deleterious. (Editorial) (2008)
  • Author(s): Takahashi M.
  • Journal Title: Cardiovasc Res 80 Pages: 5-6
  • Peer Reviewed
• [Journal Article] Deficiency of tumor necrosis factor-alpha and interferon-gamma in bone marrow cells synergistically inhibits neointimal formation following vascular injury (2008)
  • Author(s): Murayama H, Takahashi M, Takamoto M, Shiba Y, Ise H, Koyama J, Tagawa Y, Iwakura Y, Ikeda U.
  • Journal Title: Cardiovasc Res 80 Pages: 175-180
  • Peer Reviewed
• [Journal Article] Bone marrow-derived cell fuses with hepatic oval cells but are not involved in hepatic tumorgenesis in the choline-deficient ethionine-supplemented diet rat model (2008)
  • Author(s): Kubota K, Soeda J, Misawa R, Mihara M, Miwa S, Ise H, Takahashi M, Miyagawa S.
  • Journal Title: Carcinogenesis 29 Pages: 448-454
  • Peer Reviewed
• [Journal Article] Fluvastatin improves arterial stiffness in patients with coronary artery diseases and hyperlipidemia : A 5-year follow-up study (2008)
  • Author(s): Hongo M, Tsutsui H, Mawatari E, Hidaka H, Kumazaki S, Yazaki Y, Takahashi M, Kinoshita O, Ikeda U.
  • Journal Title: Circ J 72 Pages: 722-728
  • NAID: 110006680549
  • Peer Reviewed
• [Journal Article] Glucose deprivation accelerates VLDL receptor-mediated TG-rich lipoprotein uptake by AMPK activation in skeletal muscle cells (2008)
  • Author(s): Zenimaru Y, Takahashi S, Takahashi M, Yamada K, Iwasaki T, Hattori H, Imagawa M, Ueno M, Suzuki J. Miyamori I.
  • Journal Title: Biochem Biophys Res Commun 368 Pages: 716-722
  • Peer Reviewed
• [Journal Article] Alveolar bone regeneration of subcutaneously transplanted ratmolar (2008)
  • Author(s): Hosoya A, Ninomiya T, Hiraga T, Zhao C, Yoshiba K, Yoshiba N, Takahashi M, Okabe T, Wakitani S, Yamada H, Kasahara E, Ozawa H, Nakamura H.
  • Journal Title: Bone 42 Pages: 350-357
  • Peer Reviewed
• [Presentation] Role of inflammasome in cardiovascular diseases. (2010)
  • Author(s): Takahashi M.
  • Organizer: International Academy of Cardiology, 15^<th> World Congress on Heart Disease
  • Place of Presentation: Vancouver, Canada
• [Presentation] Role of inflammasome in cardiovascular diseases. (2010)
  • Author(s): Takahashi M, Taniguchi S.
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: 神戸
• [Presentation] Role of inflammasome in cardiovascular diseases. (2010)
  • Author(s): Takahashi M.
  • Organizer: International Academy of Cardiology, 15^<th> World Congress on Heart Disease
  • Place of Presentation: バンクーバー(カナダ)
• [Presentation] Th17 cells, a new subset of CD4^+ T-cells, plays an important role in angiogenic response to hindlimb ischemia. (2009)
  • Author(s): Takahashi M, Hata T, Kawaguchi M, Kashima Y, Hida S, Izawa A, Iwakura Y, Taki S, Ikeda U.
  • Organizer: 第15回日本遺伝子治療学会
  • Place of Presentation: 大阪
• [Presentation] Role of inflammasome in cardiovascular diseases. (2009)
  • Author(s): Takahashi M.
  • Organizer: The Annual Scientific Conference of the Korean Society of Lipidology and Atherosclerosis (KSLA)
  • Place of Presentation: Seoul, South Korea
• [Presentation] Deficiency of ASC (apotosis-associated speck-like protein containing a caspase recruitment domain) in bone marrow cells improved myocardial ischemia-reperfusion injury in mice. (2009)
  • Author(s): Kawaguchi M., Takahashi M, Hata T, Kashima Y, Takahashi Y, Sagara J, Taniguchi S, Ikeda U.
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: Orlando, USA
• [Presentation] Contribution of Th17 cells, a new subset of CD4^+ T cells, to angiogenic response to hindlimb ischmia. (2009)
  • Author(s): Hata T, Takahashi M, Kawaguchi M, Kashima Y, Izawa A, Hida S, Iwakuma Y, Taki S, Ikeda U.
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: Orlando, USA
• [Presentation] Inflammasome activation in cardiac fibroblasts is essential for myocardial ischemia-reperfusion injury. (2009)
  • Author(s): Kawaguchi M, Takahashi M, Hata T, Kashima Y, Takahasni, Y, Sagara J, Taniguchi S, Ikeda U.
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: Orlando, USA
• [Presentation] Deficiency of ASC (apotosis-associatde speck-like protein containing a caspase recruitment domain) in bone marrow cells improved myocardial ischemia-reperfusion injury in mice. (2009)
  • Author(s): Kawaguchi,M., Takahashi.M., Hata,T., Kashima,Y., Takahashi,Y., Sagara,J., Taniguchi,S., Ikeda,U.
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: Orlando, U.S.A.
• [Presentation] Inflammasome activation in cardiac fibroblasts is essential for myocardial ischemia-reperfusion injury. (2009)
  • Author(s): Kawaguchi,M., Takahashi,M., Hata,T., Kashima,Y., Takahasni,Y., Sagara,J., Taniguchi,S., Ikeda,U.
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: Orlando, U.S.A.
• [Presentation] Role of an Inflammasome adaptor molecule ASC in myocardial ischemia-reperfusion injury. (2008)
  • Author(s): Kawaguchi M, Takahashi M, Hata T, Takahashi Y, Morimoto H, Ise H, Sagara J, Hongo M, Taniguchi S, Ikeda U.
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: New Orleans, USA
• [Presentation] Critical role of Th17-CD4^+ T cells in angiogenic response to hindlimb ischemia in mice. (2008)
  • Author(s): Hata T, Takahashi M, Kawaguchi T, Kashima Y, Shiba Y, Ise H, Hida S, Iwakura Y, Taki S, Ikeda U.
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: New Orleans, USA
• [Presentation] Double deficiency of tumor necrosis factor-α and Interferon-γ in bone marrow-derived cells prevents neointimal formation in a murine model of vascular injury. (2008)
  • Author(s): Murayama H, Takahashi M, Shiba Y, Ise H, Takamoto M, Tagawa Y, Iwakura Y, Ikeda U.
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: New Orleans, USA
• [Presentation] Role of an Inflammasome adaptor molecule ASC in myocardial ischemia-reperfusion injury (2008)
  • Author(s): Kawaguchi M, Takahashi M, Hata T, Takahashi Y, Morimoto H, Ise H, Sagara J, Hongo M, Taniauchi S, Ikeda U.
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: New Orleans
• [Presentation] Double deficiency of tumour necrosis factor-□ and interferon-□ in bone marrow-derived cells prevents neointimal formation in a murine model of vascular injury (2008)
  • Author(s): Murayama H, Takahashi M, Shiba Y, Ise H, Takamoto M, Tagawa Y, Iwakura Y, Ikeda U.
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: New Orleans
• [Presentation] Cardioprotection of MCP-1 against ischemia/reperfusion injury is mediated through a redox oxygen species (ROS)-dependent but K_<ATP> channel-independent pathway (2008)
  • Author(s): Morimoto H, Takahashi M, Hirose M, Kawaguchi M, Ise H, Yamada M, Ikeda U.
  • Organizer: 第72回日本循環器学会
  • Place of Presentation: 福岡
• [Presentation] 自己骨髄細胞移植による難治性血管炎に対する血管新生療法 (2008)
  • Author(s): 高橋将文、石ヶ坪良明、藤本和輝、宮本正章、相澤義房、天野純、簑田清次、室原豊明、松原弘明、池田宇一
  • Organizer: 第49回日本脈管学会総会(シンポジウム)
  • Place of Presentation: 東京
• [Remarks] 研究代表者ホームページ
  • URL: http://www.jichi.ac.jp/bioimaging/
• [Remarks] 研究内容・成果に関するWebページ
  • URL: http://www.jichi.ac.jp/bioimaging/