Abstract
S1P has a critical role in vascular maturation during mammalian development. However, little is known about the role of S1P in ischemia-induced angiogenesis in adults. We investigated the effect of both exo- and endogenous S1P on angiogenesis in ischemic skeletal muscle in adult mice. Unilateral hindlimb ischemic model is a well-established in vivo angiogenesis assay system. We monitored post-ischemic angiogenesis by blood flow recovery with laser doppler imager and capillary density with anti-CD31 immunohistochemistry after surgery. First, we injected S1P into ischemic muscle everyday after surgery in C57BL6/J mice. Limb blood flow was 2.5 fold elevated in S1P(10−8M)-injected mice at day 7. Capillary density was 1.5-fold increased in S1P group at day 10. These effects were comparable to bFGF administration. Trying to create long acting S1P, we prepared the slow-release microsphere containing S1P with polylactide-co-glycotide and intramuscularly administrated it just once immediately after surgery. Mice received microsphere containing S1P increased blood flow in ischemic limb. We also examined the effect of endogenous S1P overproduction by generating sphingosine kinase 1 transgenic (SphK1-Tg) mice, and blood flow was slightly increased compared with littermate wild type mice. S1P1 receptor selective agonist SEW2871 also accelerated blood flow recovery. We showed S1P accelerates ischemia-induced angiogenesis, most likely via S1P1 receptor in adult mice. S1P and SEW2871 is a potential therapeutic for ischemic diseases. [J Physiol Sci. 2006;56 Suppl:S120]
