Immunohistochemical expression of angiogenic and immunological factors in placenta with preeclampsia and/or fetal growth restriction

Placental soluble fms-like tyrosine kinase 1 (sFlt1) release is increased in preeclampsia, which might be associated with increased shedding of Flt-1 through a disintegrin and metalloproteinase 10 (ADAM10). Here, we explored whether ADAM10 expression is regulated by hydrogen sulfide (H2S) in placenta. Pro- and active-ADAM10 expression were significantly increased in preeclamptic placentas and inversely correlated to H2S production enzymes cystathionine β-synthase and cystathionine γ-lyase expression. H2S significantly suppressed pro- and active-ADAM10 expression whilst inhibited sFlt-1 release. Knockdown of ADAM10 caused a decrease in sFlt-1 release. Our data suggest that dysregulation of H2S production may contribute to excessive Flt-1shedding in preeclampsia.