Key results
Subcutaneous administration and placenta-targeted delivery of CBX
resulted in the hallmark of PE-like features including hypertension,
proteinuria, renal damages, elevated circulatory sFlt1 level and
increased sFlt1/ PlGF in pregnant rats. These animals displayed reduced
trophoblast invasion in uterus, impaired spiral artery remodeling and
reduced placental blood flow. In vitro study showed that 11β-HSD2
dysfunction inhibited migration and invasion of the extravillous
trophoblasts and promoted sFlt1 release in syncytiotrophoblasts.
Mechanically, sFlt1 release induced by 11β-HSD2 dysfunction is mediated
by enhancement of a disintegrin and metalloprotease (ADAM)17
transcription in placenta.