PlGF

Placental growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family of signaling proteins. In humans it is encoded by the PGF gene. PlGF exists in multiple isoforms generated by alternative splicing and promoter usage, with PlGF-1 and PlGF-2 being the best characterized and most commonly secreted forms.

Expression of PlGF is highest in the placenta, particularly during pregnancy, but it is also detectable in other tissues such as heart, lung, adipose tissue, and endothelial cells. Its expression can be upregulated by hypoxic conditions and inflammatory signals. PlGF functions primarily through binding to the VEGF receptor-1 (VEGFR-1/FLT1), promoting angiogenesis and vasculogenesis. It can enhance VEGF-A–driven angiogenic responses and modulate inflammatory processes in the vascular endothelium.

Physiologically, PlGF contributes to placental vascular development and remodeling of maternal spiral arteries during pregnancy, supporting fetal growth. Dysregulation of PlGF is associated with pathological angiogenesis in various conditions, including cancer and ocular neovascular diseases, and it participates in inflammatory vascular responses.

Clinically, circulating PlGF levels rise during normal pregnancy but are reduced in certain pregnancy complications such as preeclampsia and fetal growth restriction, where levels of its decoy receptor soluble fms-like tyrosine kinase-1 (sFlt-1) are often elevated. Measuring PlGF, alone or as part of a PlGF/sFlt-1 ratio, aids in risk assessment and early diagnosis of preeclampsia. Therapeutic strategies targeting PlGF have been explored in cancer and ocular diseases, though results have been mixed and are not widely established as standard treatments.