|
Effect of UniPR1331 on in vivo angiogenesis.3D images reconstruction of SIV in Tg(fli1:EGFP)y1 zebrafish embryos in the absence (a) or in the presence (b) of U251 cells (in red). c High magnification of the image reconstruction of b showing the detail of ectopic SIV vessels converging toward U251 cells. d Evaluation of the angiogenic response: quantification of AP + ectopic sprouts are expressed as number of sprouts/embryo and cumulative length/embryo normalized in respect to noninjected embryos (number of embryos analyzed: U251 alone, 32; U251 + DMSO, 51; U251 + UniPR1331, 47). Data are the mean ± S.E.M. of three independent experiments (*P < 0.05). e Representative images of the angiogenic response used for the quantifications reported in d. Scale bar: 100 µm. f Schematic representation of the multitarget mechanisms of action of UniPR1331. By binding to Ephs, UniPR1331 inhibits VEGFR2 internalization required for downstream signaling. Simultaneously, UniPR1331 binds VEGFR2, hampering its interaction with VEGF and receptor phosphorylation. Both these inhibitions contribute to prevent phosphorylation of ERK1/2, a key second messenger for EC proangiogenic activation.
|
