Sustained release of prostaglandin E1 potentiates the impaired therapeutic angiogenesis by basic fibroblast growth factor in diabetic murine hindlimb ischemia

Yuhong Huang, Akira Marui, Hisashi Sakaguchi, Jiro Esaki, Yoshio Arai, Keiichi Hirose, Shyamal Chandra Bir, Hisanori Horiuchi, Takayuki Maruyama, Tadashi Ikeda, Yasuhiko Tabata, Masashi Komeda

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Background: Basic fibroblast growth factor (bFGF) is a potent mitogen; however, diabetes mellitus might impair its angiogenic property. Prostaglandin E1 (PGE1) is a potent vasodilator and improves endothelial function. Thus, PGE1 could potentiate the angiogenic properties of bFGF in patients with diabetes mellitus. Methods and Results: Streptozotocin-induced diabetic mice with unilateral hindlimb ischemia were randomly treated as follows: no treatment, 0.2μg of PGE1, 10μg of bFGF, and combined administration of PGE1 and bFGF. Blood perfusion was evaluated by the ratio of ischemic- to normal-limb blood perfusion. Four weeks after the treatment, the combined administration of bFGF and PGE1 increased the blood perfusion ratio as compared with single bFGF or PGE1 (77±10% vs 56±10% and 58±10%; p<0.05, respectively). A histological evaluation showed that vascular density in the combined therapy was higher than single bFGF or PGE1 (418±59 vs 306±69 and 283±71 vessels/mm2; p<0.01, respectively); the maturity in combined therapy was also higher than single bFGF or PGE1 (46±14 vs 30±14 and 28±6 vessels/mm2; p<0.01, respectively). Conclusions PGE1 potentiated the impaired angiogenic properties of bFGF in diabetic murine hindlimb ischemia. This new strategy might contribute to more effective therapeutic angiogenesis for ischemic limb in patients with diabetes.

Original languageEnglish
Pages (from-to)1693-1699
Number of pages7
JournalCirculation Journal
Volume72
Issue number10
DOIs
Publication statusPublished - 2008

Keywords

  • Angiogenesis
  • Blood flow
  • Diabetes mellitus
  • Ischemia
  • Peripheral vascular disease

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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