What is the role of soluble fms-like tyrosine kinase 1 (sFlt-1) in the pathogenesis of preeclampsia?

Updated: Nov 29, 2018
  • Author: Kee-Hak Lim, MD; Chief Editor: Ronald M Ramus, MD  more...
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Answer

Answer

The receptor sFlt-1 is a soluble isoform of Flt-1, which is a transmembrane receptor for VEGF. Although sFlt-1 lacks the transmembrane domain, it contains the ligand-binding region and is capable of binding circulating VEGF and PlGF, preventing these growth factors from binding to transmembrane receptors. Thus, sFlt-1 has an antiangiogenic effect.

In addition to angiogenesis, VEGF and PlGF are important in maintaining endothelial homeostasis. Selective knockout of the glomerular VEGF gene has been shown to be lethal in rats, whereas the heterozygotes were born with glomerular endotheliosis (the renal lesion characteristic of preeclampsia) and eventually renal failure. Furthermore, sFlt-1, when injected into pregnant rats, produced hypertension and proteinuria along with glomerular endotheliosis. [29]

In addition to animal studies, multiple studies in humans have demonstrated that excess production of sFlt-1 is associated with an increased risk of preeclampsia. In a case-control study that measured levels of sFlt-1, VEGF, and PlGF, investigators found an earlier and greater increase in the serum level of sFlt-1 in women who developed preeclampsia (21-24 wk) than in women who did not develop preeclampsia (33-36 wk), whereas the serum levels of VEGF and PlGF deceased. Furthermore, the serum level of sFlt-1 was higher in women who developed severe preeclampsia or early preeclampsia (< 34 wk) than it was in women who developed mild preeclampsia at term. [30]


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