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

• Published in: Circulation Journal 2008, Vol.72(10), pp.1693-1699
• Main Authors: Huang, Yuhong, Marui, Akira, Sakaguchi, Hisashi, Esaki, Jiro, Arai, Yoshio, Hirose, Keiichi, Bir, Shyamal Chandra, Horiuchi, Hisanori, Maruyama, Takayuki, Ikeda, Tadashi, Tabata, Yasuhiko, Komeda, Masashi
• Format: Article
• Language: English
• Subjects: Alprostadil - metabolism; Angiogenesis; Animals; Blood flow; Blood Glucose - metabolism; Blood Vessels - pathology; Diabetes mellitus; Diabetes Mellitus - drug therapy; Diabetes Mellitus, Experimental - complications; Fibroblast Growth Factor 2 - therapeutic use; Hindlimb - blood supply; Humans; Ischemia; Ischemia - prevention & control; Male; Mice; Mice, Inbred C57BL; Neovascularization, Physiologic - drug effects; Neovascularization, Physiologic - physiology; Peripheral vascular disease; Platelet Aggregation - drug effects; Platelet Count
• ISSN: 1346-9843; 1347-4820
• DOI: 10.1253/circj.CJ-07-0960

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