PlGF (placenta growth factor) is secreted primarily by villous trophoblasts and decidual cells, with circulating levels increasing during pregnancy but attenuated in preeclampsia. Alternative splicing generates multiple human PlGF isoforms (PlGFâ1, â2, â3, and -4). PlGF signals through VEGF R1/Fltâ1 and Neuropilins, while VEGF binds both VEGF R1 and R2 but signals mainly through VEGF R2. PlGF reduces binding of VEGF to VEGF R1 and increases VEGF/VEGF R2âmediated angiogenesis. It induces monocyte activation, migration, and production of inflammatory cytokines and VEGF. These activities facilitate wound and bone fracture healing and also contribute to inflammation in active sickle cell disease and atherosclerosis.