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

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.