sFlt1

sFlt-1 is a soluble isoform of vascular endothelial growth factor receptor-1 generated by alternative splicing of the FLT1 gene. It contains the VEGF-binding domains but lacks the transmembrane and intracellular kinase regions, and is secreted into circulation.

As a decoy receptor, sFlt-1 binds VEGF-A, VEGF-B, and placental growth factor (PlGF) with high affinity, reducing signaling through VEGFR-1 and VEGFR-2. By sequestering VEGF, it inhibits angiogenesis and increases vascular permeability. sFlt-1 is produced by the placenta and by some endothelial and trophoblastic cells, and can be detected in maternal blood.

In pregnancy, elevated sFlt-1 levels are associated with preeclampsia and correlate with disease severity. The sFlt-1/PlGF ratio is used clinically to aid diagnosis and risk assessment for preeclampsia. Excess sFlt-1 can contribute to maternal endothelial dysfunction, hypertension, and proteinuria, reflecting an anti-angiogenic state linked to the condition.

In cancer and other diseases, soluble VEGF receptors can limit tumor angiogenesis, and recombinant fusion proteins that mimic sFlt-1, such as aflibercept, are used as anti-angiogenic therapies. Research continues into the modulation of sFlt-1 as a potential therapeutic strategy for obstetric and oncologic indications.