Placental overexpression of soluble CORIN in preeclampsia

Am J Pathol.2020 Feb 18. pii:S0002-9440(20)30079-1. doi: 10.1016/j.ajpath.2019.12.012


Preeclampsia (PE) is a hypertensive disease of pregnancy associated with substantial maternal and fetalmorbidity and mortality. CORIN is a transmembrane type II serine protease expressed in cardiomyocytes thatconverts pro-atrial natriuretic peptide (pro-ANP) into ANP, a cardiac hormone that regulates blood pressure. High levels of soluble CORIN have been reported inpreeclampsiaand are supposed to be cardiac in origin. Wehypothesized that during pregnancy soluble CORIN is released by the syncytiotrophoblast and that increasedlevels of soluble CORIN in preeclampsia originate from placenta. Three hundred and ninety-five patients (181PE patients and 194 controls) were analyzed. High levels of soluble CORIN were confirmed in maternal bloodfrom preeclamptic pregnancies compared to controls. Differentiated primary villous cytotrophoblasts showedthat CORIN was expressed (mRNA and protein levels) and secreted by trophoblastic cells, mostly by thesyncytiotrophoblast . Finally, placental explants demonstrated a significant increase in CORIN production and secretion in PE cases compared to controls. This study demonstrates that CORIN is secreted by trophoblasticcells and that high levels of soluble CORIN in preeclampsia have a placental origin.