The recently identified placenta growth factor (PIGF) is a member of the vascular endothelial growth factor (VEGF) family of growth factors. PIGF displays a 53% identity with the platelet-derived growth factor-like region of VEGF. By alternative splicing of RNA, two PIGF isoforms are generated: PIGF131 (PIGF-1) and PIGF152 (PIGF-2). Relative to PIGF131, PIGF152 has a 21-amino acid insertion enriched in basic amino acids. Little is known at the present time about the significance and function of these proteins. To assess their potential role, we cloned the cDNAs coding for both isoforms, expressed them in mammalian cells, and purified to apparent homogeneity the recombinant proteins. Like VEGF, the PIGF isoforms are homodimeric glycoproteins. PIGF131 is a non-heparin binding protein, whereas PIGF152 strongly binds to heparin. We examined the ability of PIGF to bind to soluble VEGF receptors, Flt-1 and Flk-1/KDR, and characterized the binding of PIGF to endothelial cells. While the PIGF proteins bound with high affinity to Flt-1, they failed to bind to Flk-1/KDR. Binding of 125I-PIGF to human endothelial cells revealed two classes of sites, having high and low affinity. The high affinity site is consistent with Flt-1; the identity of the low affinity site remains to be determined. Purified PIGF isoforms had little or no direct mitogenic or permeability-enhancing activity. However, they were able to significantly potentiate the action of low concentrations of VEGF in vitro and, more strikingly, in vivo.
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