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

Circ J. 2008 Oct;72(10):1693-9. doi: 10.1253/circj.cj-07-0960. Epub 2008 Sep 1.


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, 0.2 microg of PGE1, 10 microg 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.

MeSH terms

  • Alprostadil / metabolism*
  • Animals
  • Blood Glucose / metabolism
  • Blood Vessels / pathology
  • Diabetes Mellitus / drug therapy
  • Diabetes Mellitus, Experimental / complications*
  • Fibroblast Growth Factor 2 / therapeutic use*
  • Hindlimb / blood supply*
  • Humans
  • Ischemia / prevention & control*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neovascularization, Physiologic / drug effects
  • Neovascularization, Physiologic / physiology*
  • Platelet Aggregation / drug effects
  • Platelet Count


  • Blood Glucose
  • Fibroblast Growth Factor 2
  • Alprostadil