In vivo angiogenic activity and hypoxia induction of heterodimers of placenta growth factor vascular endothelial growth factor

To investigate the in vivo angiogenic activity of placenta growth factor (PIGF) and its heterodimers with vascular endothelial growth factor (VEGF), the induction of neovascularization of these factors in the mouse cornea was studied. VEGF(165) is sufficiently potent to stimulate new capillary growth from the limbal vessels. PIGF(129)/VEGF(165) heterodimers also induce corneal neovascularization with a maximal vessel length similar to VEGF(165), but with a marked decrease of vessel density. In contrast, PIGF(129) has little or no effect in this in vivo angiogenesis assay. The expression of VEGF mRNA and protein is drastically up-regulated by hypoxia in choriocarcinoma cells, whereas expression of PIGF is not affected by the low concentration of oxygen. Up-regulation of VEGF production results in increased formation of PIGF/VEGF heterodimers in these tumor cells. Thus, hypoxia indirectly up-regulates expression levels of PIGF/VEGF heterodimers and modulates VEGF activity when these factors are co-expressed.