Basic and clinical research for therapeutic angiogenesis of the next generation

• Project/Area Number: 23591035
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Shinshu University
• Principal Investigator: IKEDA Uichi 信州大学, 医学部, 教授 (30221063)
• Co-Investigator(Kenkyū-buntansha): KOYAMA Jun 信州大学, 医学部, 准教授 (10303463) ; IZAWA Atsushi 信州大学, 医学部附属病院, 講師 (50464095) ; KASHIMA Yuichiro 信州大学, 医学部附属病院, 助教(診療) (70545722)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 糖鎖 / 血管再生 / 循環器内科学 / 幹細胞

Research Abstract

To apply the sugar chain for regenerative medicine of cardiovascular diseases, we administered N-acetyl glucosamine (GlcNAc)-modified liposome intravenously to the vascular injury model of mice, and found that GlcNAc-liposome was accumulated specifically in the vascular injury site. In addition, we started a new therapeutic angiogenesis using adipose tissue-derived stem cells (ADRC), which is less invasive compared to revascularization therapy using bone marrow cells.

Research Products

• [Journal Article] Crucial role of hyaluronan in neointimal formation after vascular injury. (2013)
  • Author(s): Kashima Y, Takahashi M, Shiba Y, Itano N, Izawa A, Koyama J, Nakayama J, Taniguchi S, Kimata K, Ikeda U.
  • Journal Title: PLoS One Volume: 8 Issue: 3 Pages: e58760-e58760
  • DOI: 10.1371/journal.pone.0058760
  • Peer Reviewed
• [Journal Article] Presence of diastolic dysfunction in patients with peripheral artery disease (2013)
  • Author(s): Yamasaki S, Izawa A, Shiba Y, Tomita T, Miyashita Y, Koyama J, Ikeda U.
  • Journal Title: Angiology Volume: 64(7) Issue: 7 Pages: 540-543
  • DOI: 10.1177/0003319713476135
  • Peer Reviewed
• [Journal Article] Prostacyclin -a potential new target for endothelial progenitor cell-mediated angiogenesis - (2013)
  • Author(s): Shiba Y, Ikeda U.
  • Journal Title: Circ J Volume: 77(4) Pages: 906-907
  • NAID: 10031138991
  • Peer Reviewed
• [Journal Article] Prostacyclin - a potential new target for endothelial progenitor cell-mediated angiogenesis -. (2013)
  • Author(s): Shiba Y, Ikeda U.
  • Journal Title: Circ J Volume: 77(4) Pages: 906-907
  • NAID: 10031138991
  • Peer Reviewed
• [Journal Article] Creation of human cardiac cell sheets using pluripotent stem cells. (2012)
  • Author(s): Matsuura K, Wada M, Shimizu T, Haraguchi Y, Sato F, Sugiyama K, Konishi K, Shiba Y, Ichikawa H, Tachibana A, Ikeda U, Yamato M, Hagiwara N, Okano T
  • Journal Title: Biochem Biophys Res Commun Volume: 425(2) Issue: 2 Pages: 321-327
  • DOI: 10.1016/j.bbrc.2012.07.089
  • Peer Reviewed
• [Journal Article] Human ES-cell-derived cardiomyocytes electrically couple and suppress arrhythmias in injured hearts. (2012)
  • Author(s): Shiba Y, Fernandes S, Zhu WZ, Filice D, Muskheli V, Kim J, Palpant NJ, Gantz J, Moyes KW, Reinecke H, Van Biber B, Dardas T, Mignone JL, Izawa A, Hanna R, Viswanathan M, Gold JD, 他5名
  • Journal Title: Nature Volume: 489(7415) Issue: 7415 Pages: 322-325
  • DOI: 10.1038/nature11317
  • Peer Reviewed
• [Journal Article] Immunoadsorption therapy reduces oxidative stress in patients with dilated cardiomyopathy. (2012)
  • Author(s): Kasai H, Kashima Y, Izawa A, Tomita T, Miyashita Y, Koyama J, Takahashi M, Yoshio T, Yazaki Y, Higuchi M, Ikeda U
  • Journal Title: WJCD Volume: 2 Issue: 04 Pages: 305-312
  • DOI: 10.4236/wjcd.2012.24048
  • Peer Reviewed
• [Journal Article] Immunoadsorption therapy reduces oxidative stress in patients with dilated cardiomyopathy. (2012)
  • Author(s): Kasai H, Kashima Y, Izawa A, Tomita T, Miyashita Y, Koyama J, Takahashi M, Yoshio T, Yazaki Y, Higuchi M, Ikeda U
  • Journal Title: World Journal of Cardiovascular Diseases Volume: 2 Pages: 305-312
  • Peer Reviewed
• [Journal Article] Early Intervention with Rosuvastation Decreases the Lipid Components of the Plaque in Acute Coronary Syndrome (2011)
  • Author(s): Otagiri K, Tsutsui H, Kumazaki S, Miyashita Y, Aizawa K, Koshikawa M, Kasai H, Izawa A, Tomita T, Koyama J, Ikeda U.
  • Journal Title: Circulation Journal Volume: 75(3) Pages: 633-641
  • Peer Reviewed
• [Journal Article] Transient pseudorestrictive pattern of transmitral flow velocity curve in patients with paroxysmal atrial fibrillation. (2011)
  • Author(s): Motoki H, Koyama J, Tomita T, Aizawa K, Kasai H, Koshikawa M, Izawa A, Kumazaki S, Takahashi M, Ikeda U.
  • Journal Title: Echocardiography Volume: 28(3) Issue: 3 Pages: 289-297
  • DOI: 10.1111/j.1540-8175.2010.01312.x
  • Peer Reviewed
• [Journal Article] Inflammasome activation of cardiac fibroblasts is effential 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 Issue: 6 Pages: 594-604
  • DOI: 10.1161/circulationaha.110.982777
  • Peer Reviewed
• [Journal Article] Critical role of Th17 cells in inflammation and neovascularization after ischaemia. (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: 90 Issue: 2 Pages: 362-372
  • DOI: 10.1093/cvr/cvq397
  • Peer Reviewed
• [Journal Article] Influence of circumferential pulmonary vein isolation for atrial fibrillation on ST elevation in patient with Brugada syndrome (2011)
  • Author(s): Tomita T , Aizawa K , Shimada K, Motoki H, Otagiri K, Koshikawa M, Kasai H, Izawa A, Kumazaki S, Tsutsui H, Koyama J, Ikeda U.
  • Journal Title: Int J Cardiol Volume: 149 Issue: 2 Pages: e82-e84
  • DOI: 10.1016/j.ijcard.2009.04.010
  • Peer Reviewed
• [Journal Article] Novel microsnare successfully used to remove small debris from the right coronary artery (2011)
  • Author(s): Miyashita Y, Saigusa T, Ikeda U.
  • Journal Title: J Invasive Cardiol Volume: Jul. 23(7)
  • Peer Reviewed
• [Journal Article] Targeting N-acetylglucosamine-bearing polymer-coated liposomes to vascular smooth muscle cells (2011)
  • Author(s): Ise M, Ise H, Shiba Y, Kobayashi S, Goto M, Takahashi M, Akaike T, Ikeda U.
  • Journal Title: J Artif Organs Volume: (4) Issue: 4 Pages: 301-309
  • DOI: 10.1007/s10047-011-0595-3
  • NAID: 10030339271
  • Peer Reviewed
• [Journal Article] Early intervention with rosuvastation decreases the lipid components of the plaque in acute coronary syndrome. (2011)
  • Author(s): Otagiri K, Tsutsui H, Kumazaki S, Miyashita Y, Aizawa K, Koshikawa M, Kasai H, Izawa A, Tomita T, Koyama J, Ikeda U.
  • Journal Title: Circulation Journal Volume: 75 Pages: 633-641
  • Peer Reviewed
• [Journal Article] Transient pseudorestrictive pattern of transmitral flow velocity curve in patients with paroxysmal atrial ibrillation. (2011)
  • Author(s): Motoki H, Koyama J, Tomita T, Aizawa K, Kasai H, Koshikawa M, Izawa A, Kumazaki S, Takahashi M, Ikeda U.
  • Journal Title: Echocardiography Volume: 28 Pages: 289-97
  • Peer Reviewed
• [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 ischaemia. (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: 90 Pages: 364-72
  • Peer Reviewed
• [Journal Article] Influence of circumferential pulmonary vein isolation for atrial fibrillation on ST elevation in patient with Brugada syndrome. (2011)
  • Author(s): Tomita T , Aizawa k, Shimada K, Motoki H, Otagiri K, Koshikawa M, Kasai H, Izawa A, Kumazaki S, Tsutsui H, Koyama J, Ikeda U.
  • Journal Title: Int J Cardiol Volume: 149
  • Peer Reviewed
• [Journal Article] Novel microsnare successfully used to remove small debris from the right coronary artery. (2011)
  • Author(s): Miyashita Y, Saigusa T, Ikeda U.
  • Journal Title: J Invasive Cardiol Volume: 23
  • Peer Reviewed
• [Journal Article] Targeting N-acetylglucosamine-bearing polymer-coated liposomes to vascular smooth muscle cells. (2011)
  • Author(s): Ise M, Ise H, Shiba Y, Kobayashi S, Goto M, Takahashi M, Akaike T, Ikeda U.
  • Journal Title: J Artif Organs Volume: 14 Pages: 301-309
  • NAID: 10030339271
  • Peer Reviewed
• [Presentation] Crucial role of hyaluronan derived from macrophages in neointimal formation after vascular injury (2013)
  • Author(s): Kashima Y, Takahashi M, Itano N, Taniguchi S, Kimata K, Ikeda U.
  • Organizer: ESC2013欧州心臓学会議
  • Place of Presentation: アムステルダム(オランダ)
• [Presentation] Predictors of long-term outcomes in patients with medical treatment for acute aortic dissection (2013)
  • Author(s): Izawa A, Hirota S, Yamaka K, Takeuchi T, Okada A, Shiba Y, Tomita T, Miyashita Y, Koyama J, Ikeda U.
  • Organizer: ESC2013欧州心臓学会議
  • Place of Presentation: アムステルダム(オランダ)
• [Presentation] The successful case of angioplasty on popliteal artery occlusion by using excimer laser atherectomy after balloon angioplasty failure (2013)
  • Author(s): Ebisawa S, Miyashita Y, Hioki H, Karube K, Yaguchi T, Abe N, Saigusa T, Miura T, Ikeda U.
  • Organizer: 第22回日本心血管インターベンション治療学会学術集会
  • Place of Presentation: 横浜
• [Presentation] Assessment of prognostic improvement by multidisciplinary therapy on patients with critical limb ischemia (2013)
  • Author(s): Hioki H, Miyashita Y, Yaguchi T, Abe N, Ebisawa S, Miura T, Tomita T, Koyama J, Ikeda U.
  • Organizer: 第22回日本心血管インターベンション治療学会学術集会
  • Place of Presentation: 横浜
• [Presentation] Assessment of prognostic improvement by multidisciplinary therapy on patients with critical limb ischemia. (2013)
  • Author(s): Hioki H, Miyashita Y, Yaguchi T, Abe N, Ebisawa S, Miura T, Tomita T, Koyama J, Ikeda U.
  • Organizer: 日本心血管インターベンション治療学会学術集会
  • Place of Presentation: 神戸国際展示場
• [Presentation] The successful case of angioplasty on popliteal artery occlusion by using excimer laser atherectomy after balloon angioplasty failure. (2013)
  • Author(s): Ebisawa S, Miyashita Y, Hioki H, Karube K, Yaguchi T, Abe N, Saigusa T, Miura T, Ikeda U.
  • Organizer: 日本心血管インターベンション治療学会学術集会
  • Place of Presentation: 神戸国際展示場
• [Presentation] Predictors of long-term outcomes in patients with medical treatment for acute aortic dissection. (2013)
  • Author(s): Izawa A, Hirota S, Yamaka K, Takeuchi T, Okada A, Shiba Y, Tomita T, Miyashita Y, Koyama J, Ikeda U.
  • Organizer: 欧州心臓学会議
  • Place of Presentation: アムステルダム（オランダ）
• [Presentation] Crucial role of hyaluronan derived from macrophages in neointimal formation after vascular injury. (2013)
  • Author(s): Kashima Y, Takahashi M, Itano N, Taniguchi S, Kimata K, Ikeda U.
  • Organizer: 欧州心臓学会議
  • Place of Presentation: アムステルダム（オランダ）
• [Presentation] Development of spontaneous myocarditis in Nuclear Factor kappa B(NFκB)p50-deficient mice : the emerging role of NFκB p65 in its pathogenesis (2012)
  • Author(s): Gautam M, Izawa A, Shiba Y, Kashima Y, Koyama J, Hongo M, Sano K, Hayashi T, Ichikawa M, Ikeda U.
  • Organizer: AHA2012アメリカ心臓協会
  • Place of Presentation: ロサンゼルス(アメリカ)
• [Presentation] Critical role of hyaluronan in neointimal formation after vascular injury in mice (2012)
  • Author(s): Kashima Y, Takahashi M, Shiba Y, Itano N, Kimata K, Izawa A, Ikeda U.
  • Organizer: AHA2012アメリカ心臓協会
  • Place of Presentation: ロサンゼルス(アメリカ)
• [Presentation] Development of spontaneous myocarditis in Nuclear Factor kappa B(NFκB)p50-deficient mice:the emerging role of NFκB p65 in its pathogenesis. (2012)
  • Author(s): Gautam Milan, Izawa A, Shiba Y, Kashima Y, Koyama J, Hongo M, Sano K, Hayashi T, Ichikawa M, Ikeda U
  • Organizer: 米国心臓病学会議
  • Place of Presentation: ロサンゼルス
• [Presentation] Critical role of hyaluronan in neointimal formation after vascular injury in mice. (2012)
  • Author(s): Kashima Y, Takahashi M, Shiba Y, Itano N, Kimata K, Izawa A, Ikeda U
  • Organizer: 米国心臓病学会議
  • Place of Presentation: ロサンゼルス
• [Presentation] Targeted Disruption of p50 Subunit of Nuclear Factor kappa B (NFB) Leads to Spontaneous Myocarditis in Mice (2011)
  • Author(s): Gotam M, Izawa A, Shiba Y, Kashima Y, Koyama J, Hongo M, Sano K, Hayashi T, Agematsu K, Ichikawa M, Ikeda U.
  • Organizer: AHA2011アメリカ心臓協会
  • Place of Presentation: オーランド(アメリカ)
• [Presentation] Specific Overexpression of Hyaluronan in Vascular Smooth Muscle Cells Augments Neointimal Formation after Vascular Injury in Mice (2011)
  • Author(s): Kashima Y, Takahashi M, Hata T, Kawaguchi M, Izawa A, Itano N, Kimata K, Ikeda U.
  • Organizer: 第75回日本循環器学会
  • Place of Presentation: 横浜
• [Presentation] Specific Overexpression of Hyaluronan in Vascular Smooth Muscle Cells Augments Neointimal Formation after Vascular Injury in Mice. (2011)
  • Author(s): Kashima Y, Takahashi M, Hata T, Kawaguchi M, Izawa A, Itano N, Kimata K, Ikeda U.
  • Organizer: 第75回日本循環器学会
  • Place of Presentation: パシフィコ横浜
• [Presentation] Targeted disruption of p50 subunit of nuclear factor kappa B (NFkB) leads to spontaneous myocarditis in mice. (2011)
  • Author(s): Gotam M, Izawa A, Shiba Y, Kashima Y, Koyama J, Hongo M, Sano K, Hayashi T, Agematsu K, Ichikawa M, Ikeda U.
  • Organizer: AHA scientific sessions 2011
  • Place of Presentation: Orlando(USA)
• [Presentation] Critical role of hyaluronan derived from vascular smooth muscle cells in neointimal formation after vascular injury. (2011)
  • Author(s): Kashima Y, Takahashi M, Hata T, Kawaguchi M, Izawa A, Itano N, Taniguchi S, Ikeda U.
  • Organizer: AHA scientific sessions 2011
  • Place of Presentation: Orlando(USA)