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Potential usage of endothelial progenitor cells (EPC) in neovascularization

Research Project

Project/Area Number 15500313
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biomedical engineering/Biological material science
Research InstitutionTokyo Medical and Dental University

Principal Investigator

YOSHIDA Masayuki  Tokyo Medical and Dental University, Associate Professor, 大学院・医歯学総合研究科, 助教授 (80282771)

Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2003: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywordsprogenitor cells / adhesion molecule / neovascularization / 血管内費前駆細胞
Research Abstract

In this project, we investigated potential usage of endothelial progenitor cells (EPC) in neovascularization especially molecular mechanisms that support their adhesion to mature vascular endothelium. In the first year of the project, we were able to establish culture system of EPC in vitro. Moreover, we conducted an adhesion assay under physiological flow condition using EPC. We found that cytokine activation of vascular endothelium significantly upregulated adhesion of EPC when compared to unactivated endothelium. When we pretreated these vascular endothelium with adhesion blocking antibodies against E-selectin, ICAM 1, and VCAM-1, anti-E-selectin antibody but not other antibodies blocked adhesion of EPC to endothelium, suggesting an important role for E-selectin in EPC adhesion. In the second year, we developed a neovascularization model using ischemic hindlimb in nude mice. Injection of EPC to these mice significantly improved their neovascularization in the hindlimb as previously reported. When amount of EPC was reduced to one-fifth of the optimal number, the recovery of blood flow was significantly attenuated. However, when adenovirus containing E-selectin cDNA was introduced to express E-selectin, neovascularization was significantly restored. These data suggested that potential efficacy of E-selectin in neovascularization.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (33 results)

All 2004 2003 Other

All Journal Article (28 results) Book (1 results) Publications (4 results)

  • [Journal Article] MCP-1-induced enhancement of THP-1 adhesion to vascular endothelium was modulated by HMG-CoA reductase inhibitor through RhoA GTPase-, but not ERK1/2-dependent pathway2004

    • Author(s)
      M.Hiraoka, N.Nitta, M.Nagai, K.Shimokado, M.Yoshida
    • Journal Title

      Life Sci. 75

      Pages: 1333-1341

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] E-Selectin Blockade Decreases Adventitial Inflammation and Attenuates Intimal Hyperplasia in Rat Carotid Arteries After Balloon Injury2004

    • Author(s)
      R.Gotoh, J.Suzuki, H.Kosuge, T.Kakuta, S.Sakamoto, M.Yoshida, M.Isobe
    • Journal Title

      Arterioscler Thromb Vasc Biol. 24

      Pages: 2063-2068

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] MCP-1-induced enhancement of THP-1 adhesion to vascular endothelium was modulated by HMG-CoA reductase inhibitor through RhoA GTPase-, but not ERK1/2-dependent pathway.2004

    • Author(s)
      M.Hiraoka, N.Nitta, M.Nagai, K.Shimokado, M.Yoshida.
    • Journal Title

      Life Sci 75

      Pages: 1333-1341

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] E-Selectin Blockade Decreases Adventitial Inflammation and Attenuates Intimal Hyperplasia in Rat Carotid Arteries After Balloon Injury.2004

    • Author(s)
      R.Gotoh, J.Suzuki, H.Kosuge, T.Kakuta, S.Sakamoto, M.Yoshida, M.Isobe.
    • Journal Title

      Arterioscler Thromb Vasc Biol. 24

      Pages: 2063-2068

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] MCP-1-induced enhancement of THP-1 adhesion to vascular endothelium was modulated by HMG-CoA reductase inhibitor through RhoA GTPase-, but not ERK 1/2-dependent pathway.2004

    • Author(s)
      M.Hiraoka, N.Nitta, M.Nagai K, Shimokado, M.Yoshida
    • Journal Title

      Life Sci. 75

      Pages: 1333-1341

    • Related Report
      2004 Annual Research Report
  • [Journal Article] E-Selectin Blockade Decreases Adventitial Inflammation and Attenuates Intimal Hyperplasia in Rat Carotid Arteries After Balloon Injury.2004

    • Author(s)
      R.Gotoh, J.Suzuki, H.Kosuge, T.Kakuta, S.Sakamoto, M.Yoshida, M.Isobe
    • Journal Title

      Arterioscler.Thromb.Vasc.Biol. 24

      Pages: 1-7

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Administration of Adenovirus E-selectin Sifnificantly Potentiates Endothelial Progenitor Cell Dependent Neovasclarization in Murine Ischemic Hindlimb Model2004

    • Author(s)
      Y.Nishiwaki, M.Yoshida H.Iwaguro, H.Masuda, T.Asahara, M.Isobe
    • Journal Title

      Circulation J.Suppl. 68

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Pretreatment of Porphyromonas Gingivalis Significantly Induced Monocyte Adhesion to Vascular Endothelium.2004

    • Author(s)
      N.Nakamura.H.Yi, Y.Inoue, M.Umeda, J.Ishikawa, T.Iwai, M.Yoshida
    • Journal Title

      Circulation J.Suppl. 68

    • Related Report
      2004 Annual Research Report
  • [Journal Article] E-Selectin-Triggered Recruitment of Endothelial Progenitor Cells to Vascular Endothelium is Significantly Enhanced by Preexisting Plateles.2004

    • Author(s)
      N.Nakamura, Y.Nishiwaki, M.Yoshida, K.Shimokado
    • Journal Title

      Circulation J.Suppl. 68

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Identification of the critical serine residues responsible for phosphorylation of endothelial E-selectin.2004

    • Author(s)
      M.Nagai, N.Nitta, K.Shimokado, M.Yoshida
    • Journal Title

      Circulation J.Suppl. 68

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Sphinsosine I-phosphate induced monocyte-endothelial interaction involves PKC and RhoA dependent mechanism2004

    • Author(s)
      A.Kawakami, M.Nagai, A.Tanaka, K.Nakajima, K.Shimokado, M.Yoshida
    • Journal Title

      Circulation J.Suppl. 68

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Fluvastatin inhibits recruitment of HIV envelope protein-triggered CD+4 I cell to vascular endothelium2004

    • Author(s)
      Y.Takano, K.Shimokado, Y.Hata, M.Yoshida
    • Journal Title

      Circulation J.Suppl. 68

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Pitavastatin Inhibits Remmnant Lipoprotein-induced Macrophage Foam Cell Formation via ApoB48 Receptor-dependent Mechanism2004

    • Author(s)
      A.Kawakami, M.Nagai, A.Tanaka, K.Nakajima, K.Shimokado, M.Yoshida
    • Journal Title

      Circulation J.Suppl. 68

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Novel Cell Delivery System <Nicrobubbles Desturuction b Ultrasound caused Angiogenesis by Transplantation of Bone Marrow Cells in Platelet Destruction-Dependent Manner>2004

    • Author(s)
      T.Imada, H.Matsubara, T.Nishiue, M.Yoshida.O.Iba.K.Amano, H.Masaki, Y.Mori, H.Kojima, Y.Nishiwaki, T.Iwasawa
    • Journal Title

      Circulation J.Suppl. 68

    • Related Report
      2004 Annual Research Report
  • [Journal Article] E-Selectin Polymorphism Associated With Myocardial Infarction Causes Enhanced Leukocyte-Endothelial Interactions Under Flow Conditions2003

    • Author(s)
      M.Yoshida, Y.Takano, T.Sasaoka, T.Izumi, A.Kimura
    • Journal Title

      Arterioscler Thromb Vasc Biol. 23

      Pages: 783-788

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Amlodipine Modulates THP-1 Cell Adhesion to Vascular Endothelium via Inhibition of Protein Kinase C Signal Transduction2003

    • Author(s)
      T.Yu, I.Morita, K.Shimokado, T.Iwai, M.Yoshida
    • Journal Title

      Hypertension 42

      Pages: 329-334

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Introduction of short interfering RNA to silence endogenous E-selection in vascular endothelium leads to successful inhibition of leukocyte adhesion2003

    • Author(s)
      Y.Nishiwaki, T.Yokota, M.Hiraoki, M.Miyagishi, K.Taira, M.Isobe, H.Mizusawa, M.Yoshida
    • Journal Title

      Biochem. Biophys. Res. Com. 310

      Pages: 1062-1066

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Pioglitazone reduces monocyte adhesion to vascular endothelium under flow by modulating RhoA GTPase and focal adhesion kinase2003

    • Author(s)
      Y.Toriumi, M.Hiraoka, M.Watanabe, M.Yoshida
    • Journal Title

      FEBS Letters 553

      Pages: 419-422

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Remnant Lipoprotein-Induced Smooth Muscle Cell Proliferation Involves Epidermal Growth Factor Receptor Transactivation2003

    • Author(s)
      A.Kawakami, A.Tanaka, T.Chiba, K.Nakajima, K.Shimokado, M.Yoshida
    • Journal Title

      Circulation 108

      Pages: 2679-2688

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Bone Marrow Monocyte Lineage Cells Adhere on Injured Endothelium in a Monocyte Chemoattractant Protein-1-Dependent Manner and Accelerate Reendothelialization as Endothelial Progenitor Cells2003

    • Author(s)
      S.Fujiyama, K.Amano, K.Uehira, M.Yoshida, Y.Nishiwaki, Y.Nozawa, D.Jin, S.Takai, M.Miyazaki, K.Egashira, T.Imada, T.Iwasaka, H.Matsubara
    • Journal Title

      Circ Res. 93

      Pages: 980-989

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Blockade of cell adhesion by a small molecule selectin antagonist attenuates myocardial ischemia/reperfusion injury2003

    • Author(s)
      Y.Onai, J.Suzuki, Y.Nishiwaki, R.Gotoh, K.Berens, R.Dixon, M.Yoshida, H.Ito, M.Isobe
    • Journal Title

      Eur J Pharmacol. 481

      Pages: 217-225

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] E-Selectin Polymorphism Associated With Myocardial Infarction Causes Enhanced Leukocyte-Endothelial Interactions Under Flow Conditions.2003

    • Author(s)
      M.Yoshida, Y.Takano, T.Sasaoka, T.Izumi, A.Kimura.
    • Journal Title

      Arterioscler Thromb Vasc Biol. 23

      Pages: 783-788

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Amlodipine Modulates THP-1 Cell Adhesion to Vascular Endothelium via Inhibition of Protein Kinase C Signal Transduction.2003

    • Author(s)
      T.Yu, I.Morita, K.Shimokado, T.Iwai, M.Yoshida.
    • Journal Title

      Hypertension 42

      Pages: 329-334

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Introduction of short interfering RNA to silence endogenous E-selectin in vascular endothelium. leads to successful inhibition of leukocyte adhesion.2003

    • Author(s)
      Y.Nishiwaki, T.Yokota, M.Hiraoka, M.Miyagishi, K.Taira, M.Isobe, H.Mizusawa, M.Yoshida.
    • Journal Title

      Biochem.Biophys.Res.Com. 310

      Pages: 1062-1066

    • NAID

      110002709233

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Pioglitazone reduces monocyte adhesion to vascular endothelium under flow by modulating RhoA GTPase and focal adhesion kinase.2003

    • Author(s)
      Y.Toriumi, M.Hiraoka, M.Watanabe, M.Yoshida.
    • Journal Title

      FEBS Letters 553

      Pages: 419-422

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Remnant Lipoprotein-Induced Smooth Muscle Cell Proliferation Involves Epidermal Growth Factor Receptor Transactivation.2003

    • Author(s)
      A.Kawakami, A.Tanaka, T.Chiba, K.Nakajima, K.Shimokado, M.Yoshida.
    • Journal Title

      Circulation 108

      Pages: 2679-2688

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Bone Marrow Monocyte Lineage Cells Adhere on Injured Endothelium in ii -Monocyte Chemoattractant Protein-1-Dependent Manner and Accelerate Reendothelialization as Endothelial Progenitor Cells.2003

    • Author(s)
      S.Fujiyama, K.Amano, K.Uehira, M.Yoshida, Y.Nishiwaki, Y.Nozawa, D.Jin, S.Takai, M.Miyazaki, K.Egashira, T.Imada, T.Iwasaka, H.Matsubara.
    • Journal Title

      Circ Res. 93

      Pages: 980-989

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Blockade of cell adhesion by a small molecule selectin antagonist attenuates myocardial ischemia/reperfusion injury.2003

    • Author(s)
      Y.Onai, J.Suzuki, Y.Nishiwaki, R.Gotoh, K.Berens, R.Dixon, M.Yoshida, H.Ito, M.Isobe.
    • Journal Title

      Eur J Pharmacol. 481

      Pages: 217-225

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] 日英対話で学ぶ米国の臨床医学(Language and Philosophy of Western Medicine)2004

    • Author(s)
      吉田 雅幸
    • Publisher
      南山堂
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] M.Yoshida, T.Sasaoka, Y.Takano et al.: "E-selectin polymorphism associated with myocardial infarction causes enhanced leukocyte-endothelial interactions under flow conditions"Arterioscler.Thromb.Vasc.Biol.. 23. 783-788 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] T.Yu, I.Morita, M.Yoshida: "Amlodipine modulates THP-1 cell adhesion to vascular endothelium under flow via inhibition of protein kinase C-dependent signal transduction"Hypertension. 42. 329-334 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Y.Nishiwaki, M.Hiraoka, M.Yoshida: "Introduction of short interfering RNA to silence endogeneous E-selectin in vascular endothedium leads to successful inhibition of leukocyte adhesion"Biochem.Biophys.Res.Com. 310. 1070-1074 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kawakami, A.Tanaka, K.Shimokado, M.Yoshida: "Remnant lipoprolein-induced smooth muscle cell proliferation involves EGF receptor transactivation"Circulation. 108. 2379-2688 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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