Fig. 7.

VEGFR1 and FGFR1 are required for the inhibitory effect of VEGF-B. a, b Western blot showing that VEGF-B (10 min treatment) inhibits FGF2-induced Erk activation in WT ECs (Control-Ad). This inhibition is lost upon Flt1 deletion (Cre-Ad). c, d Western blot showing that VEGF-B (100 ng/ml, 10 min treatment) inhibits FGF2 (50 ng/ml)-induced Erk activation in WT ECs (Control-Ad). This inhibition is lost upon Fgfr1 deletion (Cre-Ad). For (b) and (d), adjusted p values were from one-way ANOVA followed by Sidak post hoc analysis (number of comparisons, 2). The experiments were repeated three times. e, f Scheme illustrating the context-dependent effects of VEGF-B. Under conditions of high FGF2/FGFR1 levels, VEGF-B can be anti-angiogenic by inhibiting the FGF2/FGFR1 pathway, such as in tumors characterized by abundant FGF2/FGFR1 expression (e). Under conditions of low/no FGF2/FGFR1 expression, such as in tissue/blood vessel disintegration (e.g., myocardial infarction or blood vessel regression after FGF2 withdrawal), VEGF-B can be pro-angiogenic due to its known anti-apoptotic and survival effects (f). Therefore, depending on FGFR1/FGF2 levels, VEGF-B can be anti- or pro-angiogenic depending on the specific condition