Inhibition of angiopoietin-1 (ANGPT1) affects vascular integrity in ovarian hyperstimulation syndrome (OHSS).

L SCOTTI; D ABRAMOVICH; N PASCUALI; L HARO DURAND; G IRUSTA; I DE ZÚÑIGA; M. TESONE; F. PARBORELL

REPRODUCTION FERTILITY AND DEVELOPMENT

CSIRO PUBLISHING

Lugar: Collingwood; Año: 2014

1031-3613

Ovarian hyperstimulation syndrome (OHSS) is a complication of ovarian stimulation with gonadotrophinsfollowing human chorionic gonadotrophin (hCG) administration. The relationship between hCG and OHSS is partlymediated via the production of angiogenic factors, such as vascular endothelial growth factor A (VEGFA) andangiopoietins (ANGPTs). Here, we investigated the effect of ANGPT1 inhibition on ovarian angiogenesis in follicularfluid (FF) from women at risk of OHSS, using the chorioallantoic membrane (CAM) of quail embryos as an experimentalmodel. We also analysed cytoskeletal changes and endothelial junction protein expression induced by this FF in thepresence or absence of an ANGPT1-neutralising antibody in endothelial cell cultures. The presence of this antibodyrestored the number of vascular branch points and integrin avb3 levels in the CAMs to control values. ANGPT1 inhibitionin FF from OHSS patients also restored the levels of claudin-5, vascular endothelial cadherin and phosphorylatedb-catenin and partially reversed actin redistribution in endothelial cells. Our findings suggest that ANGPT1 increasespathophysiological angiogenesis in patients at risk of OHSS by acting on tight and adherens junction proteins. Elucidatingthe mechanisms by which ANGPT1 regulates vascular development and cell?cell junctions in OHSS will contribute toidentifying new therapeutic targets for the treatment of human diseases with aberrant vascular leakage