Abstract
S1P has a critical role in vascular maturation in vivo during mammalian development. However, little is known about the therapeutic effect of S1P in ischemia-induced angiogenesis in adults. We investigated the effect of exogeneous S1P on angiogenesis in ischemic skeletal muscle in adult mice. Unilateral murine hindlimb ischemic model is an well-established in vivo angiogenesis assay system. We evaluated post-ischemic angiogenesis by monitoring post-surgical blood flow recovery with a laser doppler imager and the capillary density with anti-CD31 immunohistochemistry. First, we injected S1P solution into the ischemic muscle everyday during 28 days after surgery in C57BL6/J mice. The limb blood flow was significantly elevated between 10 and 28 days after surgery in S1P-injected mice compared to vehicle-injected mice. The capillary density was significantly increased in the S1P-administered group at 10 days after surgery. Next, we administrated several different doses of S1P into the ischemic lesion everyday. S1P accelerated recovery of the blood flow from ischemia and induced an increase in the capillary density in a dose-dependent manner. bFGF is known to be one of the most potent angiogenic factors, daily injection of bFGF increased the blood flow and the capillary density in the ischemic limb. The comparison of the effects between S1P and bFGF showed that S1P stimulated ischemia-induced angiogenesis to the similar extent of bFGF. These results suggest the possibility that S1P could be a potential therapeutic agent for ischemic diseases. [J Physiol Sci. 2007;57 Suppl:S122]
