O19. Decreased plasma hemopexin activity in preeclampsia is associated with decreased plasma AT-1 receptor levels and increased placental and monocyte AT-1 receptor expression

Abstract

Introduction Hemopexin (Hx), apart from being a free heme scavenger, also has protease activity. While during healthy pregnancy, Hx activity was increased as compared with non-pregnant individuals, in preeclampsia, Hx activity was decreased as compared with healthy pregnant women. Since we have previously shown that active Hx was able to shed the angiotensin II type 1 receptor (AT-1R) from various cell types in vitro , we now hypothesized that the increased Hx activity in pregnancy leads to increased shedding of the AT-1R from the vascular wall and subsequently decreased angiotensin II sensitivity. In preeclampsia the decreased Hx activity may lead to decreased shedding of the AT-1R and therefore increased angiotensin II activity. Objective We aimed to evaluate whether decreased Hx activity in preeclampsia was associated with increased AT-1R expression (on placental tissue and monocytes) and reduced presence of the AT-1R in the circulation. Methods We obtained peripheral blood samples from non pregnant ( n =21), healthy pregnant ( n =25) and (early onset) preeclamptic ( n =26) women. We measured plasma Hx activity (colorimetric assay) and plasma AT-1R levels (Western blotting) and monocyte AT-1R expression (flow cytometry). From another group of healthy pregnant ( n =15) and (early onset) preeclamptic women ( n =24), we collected placental biopsies, in which we measured placental AT-1R expression using immunohistochemistry and qPCR. Results The increase in plasma Hx activity in healthy pregnant women vs non-pregnant women ( p p p p p p p Conclusions Our data suggest that also in vivo active Hx sheds the AT-1R from tissues, such as monocytes and placenta. Therefore active Hx may play a role in the development of the decreased responsiveness to angiotensin II in healthy pregnancy, while the decreased Hx activity in preeclampsia may contribute to increased angiotensin II sensitivity in this disease.