Prostacyclin Stimulated Integrin-Dependent Angiogenic Effects of Endothelial Progenitor Cells and Mediated Potent Circulation Recovery in Ischemic Hind Limb Model

• Aburakawa Yoko

  Division of Cardiovascular, Respiratory and Neurology, Asahikawa Medical University

• Kawabe Jun-ichi

  Department of Cardiovascular Regeneration and Innovation, Asahikawa Medical University

• Okada Motoi

  Division of Cardiovascular, Respiratory and Neurology, Asahikawa Medical University

• Yamauchi Atsushi

  Division of Cardiovascular, Respiratory and Neurology, Asahikawa Medical University

• Asanome Akira

  Division of Cardiovascular, Respiratory and Neurology, Asahikawa Medical University

• Kabara Maki

  Division of Cardiovascular, Respiratory and Neurology, Asahikawa Medical University

• Matsuki Motoki

  Division of Cardiovascular, Respiratory and Neurology, Asahikawa Medical University

• Takehara Naofumi

  Department of Cardiovascular Regeneration and Innovation, Asahikawa Medical University

• Nakagawa Naoki

  Division of Cardiovascular, Respiratory and Neurology, Asahikawa Medical University

• Okumura Shunsuke

  Division of Cardiovascular, Respiratory and Neurology, Asahikawa Medical University

• Minami Yoshinori

  Division of Cardiovascular, Respiratory and Neurology, Asahikawa Medical University

• Mizukami Yusuke

  Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University

• Yuhki Koh-ichi

  Department of Pharmacology, Asahikawa Medical University

• Ushikubi Fumitaka

  Department of Pharmacology, Asahikawa Medical University

• Hasebe Naoyuki

  Department of Cardiovascular Regeneration and Innovation, Asahikawa Medical University Division of Cardiovascular, Respiratory and Neurology, Asahikawa Medical University

抄録

Background: Prostacyclin (PGI₂) enhances angiogenesis, especially in cooperation with bone marrow (BM)-derived endothelial progenitor cells (EPCs). However, the mechanisms of PGI₂ in EPC-mediated angiogenesis in vivo remain unclear. The purpose of this study was to clarify the role of PGI₂ in EPC-mediated angiogenesis using BM-specific IP deletion mice. Methods and Results: Hind limb ischemia (HLI) was induced in wild-type (WT) mice transplanted with IP-deleted BM (WT/BM(IP^–/–). Recovery of blood flow (RBF) in WT/BM(IP^–/–) was impaired for 28 days after HLI, whereas RBF in IP^–/–/BM(WT) was attenuated for up to 7 days compared with WT/BM(WT). The impaired RBF in WT/BM(IP^–/–) was completely recovered by intramuscular injection of WT EPCs but not IP^–/– EPCs. The impaired effects of IP^–/– EPCs were in accordance with reduced formation of capillary and arterioles in ischemic muscle. An ex vivo aortic ring assay revealed that microvessel formation was enhanced by accumulation/adhesion of EPCs to perivascular sites as pericytes. IP^–/–EPCs, in which expression of integrins was decreased, had impaired production of angiogenic cytokines, adhesion to neovessels and their angiogenic effects. The small-interfering RNA (siRNA)-mediated knockdown of integrin β1 in WT EPCs attenuated adhesion to microvessels and their in vivo and in vitro angiogenic effects. Conclusions: PGI₂ may induce persistent angiogenic effects in HLI through adhesion of EPCs to perivascular sites of neovessels via integrins in addition to paracrine effects.  (Circ J 2013; 77: 1053–1062)<br>

収録刊行物

• Circulation Journal

  Circulation Journal 77 (4), 1053-1062, 2013

  一般社団法人 日本循環器学会

キーワード

• Angiogenesis
• Endothelial progenitor cells
• Hind limb ischemia
• Prostacyclin

詳細情報

• CRID: 1390282680080118656
• NII論文ID: 10031139011
• NII書誌ID: AA11591968
• DOI: 10.1253/circj.cj-12-0897
• COI: 1:STN:280:DC%2BC3s3js1GqtA%3D%3D
• ISSN: 13474820
• ISSN: 13469843
• PubMed: 23257313
• Web Site: https://asahikawa-med.repo.nii.ac.jp/records/4539
• Web Site: https://www.jstage.jst.go.jp/article/circj/77/4/77_CJ-12-0897/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2014027921
• 本文言語コード: en
• データソース種別:
  • JaLC
  • IRDB
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
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