Sustained Release of Prostaglandin E₁ Potentiates the Impaired Therapeutic Angiogenesis by Basic Fibroblast Growth Factor in Diabetic Murine Hindlimb Ischemia

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, 0.2 μg of PGE₁, 10 μg 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. (Circ J 2008; 72: 1693 - 1699)