抄録
S1P plays a critical role in vascular maturation in vivo during the mammalian development. Recently, we demonstrated for the first time that S1P stimulated neo-angiogenesis in ischemic hindlimbs of mice. In the previous study, we daily injected S1P solution locally into the hindlimb muscle. In the present study, we successfully generated a slow release type of S1P by taking advantage of three different poly(lactic-co-glycolic-acid)(PLGAs), and tested its efficacy in the mouse ischemic hindlimb where femoral artery was ligated and removed unilaterally. The amounts of S1P released from S1P-containing PLGA microparticles in a physiological medium were quite constant over 15 days in PLGA 5005. In contrast, S1P release from PLGA7505 and PLGA7510 with longer half lives than PLGA5005 sharply declined after the initial burst. Local injections of PLGA5005-S1P microparticles every 3 days, but not PLGA7505-S1P or PLGA7510-S1P, into ischemic muscle stimulated the blood flow recovery over 28 days after femoral arteriectomy, as determined with a laser Doppler imager. PLGA5005-S1P was effective in the wide range of doses. In contrast, PLGA7505-S1P and PLGA7510-S1P were less effective or non-effective in stimulating the blood flow recovery. Injections of PLGA5005-S1P stimulated angiogenesis, as determined with anti-CD31 immunohistochemistry. These results suggested that PLGA5005-S1P could be potentially useful as a therapeutic agent for stimulating post-ischemic angiogenesis. [J Physiol Sci. 2008;58 Suppl:S52]
