PURIFICATION AND CHARACTERIZATION OF A NATURALLY-OCCURRING VASCULAR ENDOTHELIAL GROWTH-FACTOR PLACENTA GROWTH-FACTOR HETERODIMER

Vascular endothelial growth factor (VEGF) is a potent and selective mi togen for endothelial cells that is angiogenic in vivo and induced by hypoxia, A homologous protein, placenta growth factor (PlGF), is also reported to be mitogenic for endothelial cells in culture, The rat GS- SL glioma cell line produces not only VEGF homodimers but also PlGF ho modimers and a novel heterodimer composed of VEGF and PlGF subunits, A ll three dimeric forms were purified to apparent homogeneity, and thei r structures and mitogenic activities were compared, VEGF . PlGF heter odimers are vascular endothelial cell mitogens nearly as potent as VEG F homodimers, Therefore, some of the biological activities attributed to VEGF homodimers might be mediated by VEGF . PlGF heterodimers. In c ontrast, pure PlGF homodimers are mitogenic for endothelial cells only at high, possibly non-physiologic concentrations; thus the biological relevance of their mitogenic activity for these cells is not obvious, However, the existence of not only homodimers but also heterodimers c learly extends the similarity between the VEGF/PlGF and the homologous platelet-derived growth factor systems.