10. Angiotensin II modulates the pathogenesis of preeclampsia through sflt-1 production from extravillous cytotrophoblast

Abstract

Introduction Preeclampsia (PE) is characterized by disturbed extravillous trophoblast migration toward uterine spiral arteries leading to increased uteroplacental vascular resistance and by vascular dysfunction resulting in reduced systemic vasodilatory property. It is known that such pathogenesis is mediated by soluble fms related tyrosine kinase 1 (sFlt-1) and Endoglin (sEng). Our objective was to evaluate the effect of angiotensin II (AngII) on the production of sFlt-1 and sEng from cytotrophoblast. Methods Plasma concentration of sFlt-1 and sEng in our PE model mouse was calculated with AngII receptor subtype 2 (AT2) stimulator (C21). Jar cell and HTR-8 cell was cultured and stimulated by AngII with or without AngII receptor subtype 1 (AT1) inhibitor and AT2 inhibitor. The concentration of sFlt-1 and sEng was calculated in culture medium of the cells using ELISA. Results C21 reduced plasma concentration of sFlt-1 resulted in improved hypertension and proteinuria but did not affect that of sEng. sFlt-1 concentration in the medium of HTR-8 was reduced by AT1 inhibitor and stimulated by AT2 inhibitor. sFlt-1 production of Jar cell could not be responded by AngII. Conclusions This study demonstrated that extravillous trophoblast (HTR-8) could produce sFlt-1 in response to AT1 and AT2; however, cytotrophoblast (Jar) could not be responded by AngII. It is suggested that extravillous trophoblast could be involved in the pathogenesis of PE through the effect of AngII and C21 could be a candidate of new therapy pf PE.