Study on effective mechanism of mycophenolic acid on antiangiogeneses in flk-GFP zebrafish

Objective To identify small molecules with potential of anti-angiogenesis (mycophenolic acid, MPA) from approved drugs and do further study for its mechanism of action. Methods The flk-GFP zebrafish serves as a model for rapid observation of angiogenesis in living embryos. We screened 1120 compounds library and revealed that MPA exhibited effect of inhibition of blood vessels but had no other detrimental effects on general embryonic development. The mechanism of MPA action was further analyzed by microangiographic studies and 3 subtypes IMP-DH, the possible target of MPA, morpholino oligos (MO) - knock. Results The inhibition of angiogenesis caused by MPA is dose-dependent. The circulation of these embryos was also blocked as revealed by microangiographic analysis, suggesting potent inhibition of angiogeneses. It was showed that IMPDH2 is mainly expressed in the ventral regions of the developing trunk and IMPDH2 antisense morpholino can inhibit angiogenesis of zebrafish (n>100, 50% showed phenotype). Conclusion MPA can induce antiangiogenesis by inhibiting IMPDH2.