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

SCOTTI LEOPOLDINA; ABRAMOVICH DALHIA; PASCUALI NATALIA; HARO DURAND LUIS; IRUSTA GRISELDA; DE ZUÑIGA IGNACIO; TESONE MARTA; PARBORELL FERNANDA

Congreso; Gordon Conference; 2013

Ovarian hyperstimulation syndrome (OHSS) is a complication of ovarian stimulation with gonadotropins following human chorionic gonadotropin (hCG) administration. The relationship between hCG and OHSS is in part mediated via angiogenic factor production, such as vascular endothelial growth factor (VEGFA) and angiopoietins (ANGPTs). Our aim was to investigate the effect of ANGPT1 inhibition in follicular fluid (FF) from women at risk of OHSS on the chorioallantoic membrane (CAM) of quail embryos as an experimental model of ovarian angiogenesis. We also analyzed cytoskeletal changes and endothelial junction protein expression induced by these FF in the presence or absence of ANGPT1 neutralizing antibody. ANGPT1 antibody addition to FF from OHSS patients restored the number of vascular branch points in the CAMs and αvβ3 integrin levels to control values. ANGPT1 inhibition in OHSS patients FF also restored endothelial claudin-5, VE-cadherin and phosphorylated β-catenin levels and partially reversed actin redistribution. Our findings suggest that ANGPT1 increases patho-physiological angiogenesis in patients at risk of OHSS by acting on tight and adherens junction proteins. Finally, elucidating the mechanisms by which ANGPT1 regulates vascular development and cell-cell junctions in OHSS will contribute to identify new therapeutic targets for the treatment of human diseases with aberrant vascular leakage.