Placenta growth factor (PlGF) is a member of the PDGF/VEGF family of growth factors that share a conserved pattern of eight cysteines [1, 2]. Alternative splicing results in at least three human mature PlGF forms containing 131 (PlGF-1), 152 (PlGF-2), and 203 (PlGF-3) amino acids (aa) respectively [1, 2]. Only PlGF-2 contains a highly basic heparin-binding 21 aa insert at the C-terminus [1]. Human PlGF-1 shares 56%, 55%, 74% and 95% aa identity with the comparable isoform of mouse, rat, canine, and equine PlGF, respectively. PlGF is mainly found as variably glycosylated, secreted, 55-60 kDa disulfide linked homodimers [3]. Mammalian cells expressing PlGF include villous trophoblasts, decidual cells, erythroblasts, keratinocytes, and some endothelial cells [1, 4-6]. Circulating PlGF increases during pregnancy, reaching a peak in mid-gestation; this increase is attenuated in preeclampsia [7]. However, deletion of PlGF in the mouse does not affect development or reproduction. Postnatally, mice lacking PlGF show impaired angiogenesis in response to ischemia [8].PlGF binds and signals through VEGF R1/Flt-1 but not VEGF R2/Flk-1/KDR, while VEGF binds both but signals only through the angiogenic receptor, VEGF R2. PlGF and VEGF therefore compete for binding to VEGF R1, allowing high PlGF to discourage VEGF/VEGF R1 binding and promote VEGF/VEGF R2-mediated angiogenesis [1, 4, 8, 9]. However, PlGF (especially PlGF-1) and some forms of VEGF can form dimers that decrease the angiogenic effect of VEGF on VEGF R2 [3, 4]. PlGF-2, but not PLGF-1, shows heparin-dependent binding of Neuropilin (Npn)-1 and Npn-2 [10, 11]..
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