OS 05-07 ROLE OF SOLUBLE ENDOGLIN IN THE PHYSIOPATHOLOGY OF PREECLAMPSIA

Abstract

Objective: Preeclampsia, characterized by hypertension and proteinuria occurring after the twentieth week of pregnancy, is a major contributor to maternal and perinatal morbidity and mortality in developed countries. The mechanisms mediating the pathogenesis preeclampsia are far from clear. Strong experimental evidence suggests that placental ischemia, resulting from the inappropriate remodeling of the maternal spiral arteries, stimulates the release of soluble factors causing hypertension and renal damage. Plasma levels of soluble endoglin (sEng) are increased before the clinical onset of preeclampsia, and we have shown that rodents exposed to high circulating levels of sEng show severe preeclampsia-like symptoms (Valbuena-Diez et al, Circulation 2012,126:2612). The purpose of this study is to evaluate if sEng plays some role in the development of preeclampsia. Design and Method: Transgenic mice overexpressing human sEng (sEng + ) were generated. Wild-type (WT) female mice were crossed with sEng + (sEng pregnant) or with WT male (WT pregnant). We measured plasma levels of sEng (ELISA), arterial pressure (tail cuff and telemetry), proteinuria, fetal mass, the histological structure of the placentas at 18th day of pregnancy, and the effect of sEng in the proliferating (MTT) and invading (transwell) ability of trophoblasts in culture. Results: Plasma levels of sEng increased in plasma of sEng pregnant from the 11th day of pregnancy, with a peak on day 13. Systolic pressure was higher in sEng than in WT pregnant mice from the 13th day of gestation and remained increased until delivery. Proteinuria was higher in sEng than in WT pregnant mice. Total fetal weight was lower in sEng than in WT pregnant mice. Placentas from sEng pregnant females showed marked vacuolization and necrosis areas. Incubation with sEng reduced the proliferation, migration and invasiveness of cultured human trophoblasts. Conclusions: Soluble endoglin plays a major role in preeclampsia shown by WT female carrying sEng + fetuses.