Abstract 2190: Local Sustained Release of Prostaglandin E1 (PGE1) may Induce both Angiogenesis and Arteriogenesis in Murine Ischemic Limb
Introduction : PGE1 is well known as a potent vasodilator clinically. Recently PGE1 is reported to induce VEGF expression in endothelial cells in vitro. However, when administered in its free form, the effect might be limited because of its rapid clearance in vivo. Therefore, local sustained release of PGE1 may induce angiogenesis and its vasodilative effects may also induce arteriogenesis.The purpose of this study was to develop a sustained release system of PGE1, and to investigate whether the system can achieve sufficient neovascularization in murine ischemic limb.
Methods : Polylactide-co-glycolide (PLGA) was used as a sustained release carrier for PGE1 for 2 weeks. Unilateral hind limb ischemia was created in C57BL/6 mice. They were randomized into five groups (n=8 each): no treatment (Control group), daily systemic administration of PGE1 solution for 14 days (total 100μg/kg: Free PGE1 group), single intramuscular injection of the PLGA containing PGE1 10, 30, and 100 μg/kg of PGE1 (10, 30, and 100 PGE1/PLGA groups, respectively). Four weeks after the treatment, hindlimb blood flow was evaluated by laser Doppler perfusion image index (ratio of ischemic-to- normal-limb blood flow). Vascular density (angiogenesis; stained with anti von Willebrand factor) and the number of mature vessels with a significant smooth muscle layer (arteriogenesis; stained with anti-α-smooth muscle action staining) were evaluated. In addition, at 1 and 3days after ligation, endogenous VEGF expression in the ischemic limbs was measured by ELISA (n=4 each).
Results : (Table⇓) Angiogenesis and arteriogenesis was dose-dependently induced by sustained release of PGE1 but not induced by systemic administration of PGE1. 100PGE1/PLGA showed a significant increase in VEGF induction as compared to Control.
Conclusion : Local sustained release of PGE1 might be a promising option of therapeutic angiogeneis for critical limb ischemia, since it has both angiogenic and arteriogenic properties.