Local Sustained Release of Prostaglandin E1 Induces Neovascularization in Murine Hindlimb Ischemia

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概要

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• Background: Although intravenous administration of prostaglandin E1 (PGE1) is commonly used in the treatment of peripheral arterial disease, it rapidly becomes inactivated in the lung. Whether local administration of sustained-release (SR) PGE1 enhances neovascularization in murine hindlimb ischemia was investigated. Methods and Results: Poly lactide-co-glycolide (PLGA) microspheres were the 4-week SR carrier of PGE1. C57BL/6 mice with unilateral hindlimb ischemia were randomly treated as follows: no treatment (Group N); single administration of 100 μg/kg PGE1 solution (Group L) into the ischemic muscles; daily systemic administration of PGE1 for 2 weeks at a total dose 100 μg/kg (Group S); and single administration of PGE1-100 μg/kg-loaded PLGA (Group P100) into the ischemic muscles. The blood perfusion in Group P100 was higher than in Groups N, L and S (ischemic/nonischemic blood perfusion ratio 88 ±11% vs 73 ±11% (P<0.01), 77 ±9% (P<0.05), 79 ±11% (P<0.05), respectively). Vascular density and αSMA-positive-vessel density in Group P100 were higher than in Groups N, L and S (vascular density (vessels/m2): 241 ±39 vs 169 ±49 (P<0.01), 169 ±54 (P<0.01), 201 ±42 (P<0.05), respectively; αSMA-positive-vessel density (vessels/m2): 34 ±10 vs 18 ±6 (P<0.01), 21 ±11 (P<0.01), 22 ±10 (P<0.01), respectively) Conclusions: Local administration of a single dose of SR PGE1 enhances neovascularization in mice hindlimb ischemia more efficiently than daily systemic administration.

• 2009-06-20

著者

• SAKATA Ryuzo

  Department of Cardiovascular Surgery, Graduate School of Medicine, Kagoshima University

• IKEDA Tadashi

  Department of Surgery, Keio University School of Medicine

• Chandra Bir

  Department Of Cardiovascular Surgery Kyoto University Graduate School Of Medicine

• Marui Akira

  Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University

• Sakaguchi Hisashi

  Department Of Cardiovascular Surgery Kyoto University Graduate School Of Medicine

• Sakaguchi Hisashi

  Department Of Cardiovascular Surgery Graduate School Of Medical Sciences Kumamoto University

• Sakata Ryuzo

  Department Of Cardiovascular Surgery Graduate School Of Medicine Kyoto University

• Miura Aya

  Dep. Of Cardiovascular Medicine Graduate School Of Medicine Dentistry And Pharmaceutical Sciences Ok

• Sakata Ryuzo

  Department Of Cardiovascular Surgery Kyoto University Graduate School Of Medicine

• Akao Masaharu

  Department Of Cardiovascular Surgery Kyoto University Graduate School Of Medicine

• Akao Masaharu

  Department Of Cardiovascular Medicine Kyoto University Graduate School Of Medicine

• Arai Yoshio

  Department Of Cardiovascular Surgery Kyoto University Graduate School Of Medicine

• Huang Yuhong

  Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine

• Esaki Jiro

  Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine

• Ikeda Tadashi

  Department Of Cardiovascular Surgery Kyoto University Graduate School Of Medicine

• TSUBOTA Hideki

  Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine

• KANAJI Toshiya

  Research Headquarters, Ono Pharmaceutical Company

• Marui Akira

  Department Of Cardiovascular Medicine Graduate School Of Medicine Kyoto University

• Marui Akira

  Department Of Cardiovascular Surgery Kyoto University Graduate School Of Medicine

• Matsumori A

  The Third Division Department Of Internal Medicine Kyoto University And Department Of Medicine Beth

• Esaki Jiro

  Department Of Cardiovascular Surgery Kyoto University Graduate School Of Medicine

• Huang Yuhong

  Department Of Cardiovascular Surgery Kyoto University Graduate School Of Medicine

• Kanaji Toshiya

  Research Headquarters Ono Pharmaceutical Company

• Tsubota Hideki

  Department Of Cardiovascular Surgery Kyoto University Graduate School Of Medicine

• Tsubota Hideki

  Department Of Cardiovascular Surgery Akane Foundation Tsuchiya General Hospital

• Arai Masazumi

  Department Of Cardiovascular Surgery Kyoto University Graduate School Of Medicine

• Matsumori Akira

  Japanese Circulation Society Guideline Preparation Group Myocarditis

• Ishii Takahiro

  Department Of Cardiovascular Surgery Kyoto University Graduate School Of Medicine

• Arai Yoshio

  Department Of Bacteriology Saitama Medical School

• Marui Akira

  Division Of Cardiology Kyoto Medical Center National Hospital Organization

• Sakata Ryuzo

  Department Of Cardiovascular Surgery Division Of Bioinformatics And Chemical Genomics Graduate Schoo

• Ikeda Tadashi

  Department Of Cardiovascular Surgery Graduate School Of Medicine Kyoto University

• Sakaguchi Hisashi

  Department Of Cardiovascular Surgery Graduate School Of Medical Science Kumamoto University

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