Résumé
Preeclampsia (PE) is a hypertensive disease of pregnancy associated with substantial maternal and fetal morbidity and mortality. Corin is a transmembrane type II serine protease expressed in the cardiomyocytes that converts pro-atrial natriuretic peptide (pro-ANP) into ANP, a cardiac hormone that regulates blood pressure. High levels of soluble corin (sCorin) have been reported in preeclampsia and are supposed to have cardiac origin. The hypothesis of our study was that during pregnancy sCorin is released by the syncytiotrophoblast, and that increased levels of sCorin in preeclampsia are of placental origin.
Soluble corin levels were measured in plasma of 375 patients from ECLAXIR study (181 PE and 194 controls) using an ELISA kit (R&D Systems). Primary cytotrophoblasts (VCT) were isolated from human term placenta (n=3), and cultured up to 72h. Cell supernatants and cells were collected and stored at -80°C. Placental villi from PE patients (n=3) and controls (n=3) were either cultured for 24h where the explant supernatants were collected and stored at -80°C, or snap-frozen and stored at -80°C, or PFA-fixed and embedded in paraffin. mRNA and protein levels of Corin were quantified by RT-qPCR, Western Blot and immunohistochemistry.
On 395 patients (181 PE and 194 controls), the high levels of sCorin in maternal blood were confirmed from preeclamptic pregnancies compared to controls. Next, experiments on differentiated primary cytotrophoblasts (VCT) showed that Corin was expressed (mRNA and protein levels) and secreted by trophoblastic cells, mostly by the syncytiotrophoblast (ST). Finally, using placental explants, a significant increase in Corin production and secretion was observed in PE cases compared to controls.
This study demonstrates that Corin is secreted by trophoblastic cells and that high levels of sCorin in preeclampsia are of a placental origin.