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

2016 ◽  
Vol 28 (6) ◽  
pp. 690 ◽  
Author(s):  
Leopoldina Scotti ◽  
Dalhia Abramovich ◽  
Natalia Pascuali ◽  
Luis Haro Durand ◽  
Griselda Irusta ◽  
...  
Keyword(s):  
At Risk ◽  
Ovarian Hyperstimulation Syndrome ◽  
Chorioallantoic Membrane ◽  
Adherens Junction ◽  
Integrin Αvβ3 ◽  
Cell Junctions ◽  
Ovarian Hyperstimulation ◽  
Vascular Endothelial ◽  
Branch Points ◽  
Junction Protein

Ovarian hyperstimulation syndrome (OHSS) is a complication of ovarian stimulation with gonadotrophins following human chorionic gonadotrophin (hCG) administration. The relationship between hCG and OHSS is partly mediated via the production of angiogenic factors, such as vascular endothelial growth factor A (VEGFA) and angiopoietins (ANGPTs). Here, we investigated the effect of ANGPT1 inhibition on ovarian angiogenesis in follicular fluid (FF) from women at risk of OHSS, using the chorioallantoic membrane (CAM) of quail embryos as an experimental model. We also analysed cytoskeletal changes and endothelial junction protein expression induced by this FF in the presence or absence of an ANGPT1-neutralising antibody in endothelial cell cultures. The presence of this antibody restored the number of vascular branch points and integrin αvβ3 levels in the CAMs to control values. ANGPT1 inhibition in FF from OHSS patients also restored the levels of claudin-5, vascular endothelial cadherin and phosphorylated β-catenin and partially reversed actin redistribution in endothelial cells. Our findings suggest that ANGPT1 increases pathophysiological angiogenesis in patients at risk of OHSS by acting on tight and adherens junction proteins. Elucidating the mechanisms by which ANGPT1 regulates vascular development and cell–cell junctions in OHSS will contribute to identifying new therapeutic targets for the treatment of human diseases with aberrant vascular leakage.

scholarly journals Lysophosphatidic Acid Up-Regulates Expression of Interleukin-8 and -6 in Granulosa-Lutein Cells through Its Receptors and Nuclear Factor-κB Dependent Pathways: Implications for Angiogenesis of Corpus Luteum and Ovarian Hyperstimulation Syndrome

2008 ◽  
Vol 93 (3) ◽  
pp. 935-943 ◽  
Author(s):  
Shee-Uan Chen ◽  
Chia-Hung Chou ◽  
Hsinyu Lee ◽  
Chi-Hong Ho ◽  
Chung-Wu Lin ◽  
...  
Keyword(s):  
Growth Factor ◽  
Lysophosphatidic Acid ◽  
Ovarian Hyperstimulation Syndrome ◽  
Umbilical Vein ◽  
Nuclear Factor Κb ◽  
Ovarian Hyperstimulation ◽  
Vascular Endothelial ◽  
Nuclear Factor ◽  
Lpa Receptors ◽  
Endothelial Growth Factor

Abstract Context: Lysophosphatidic acid (LPA) was found at significant amounts in follicular fluid of preovulatory follicle. The lysophospholipase D activity of serum from women receiving ovarian stimulation was higher than women with natural cycles. Angiogenic cytokines, including IL-6, IL-8, and vascular endothelial growth factor, increased in plasma and ascites of patients with ovarian hyperstimulation syndrome. The role of LPA in ovarian follicles is unclear. Objective: Our objective was to investigate the expression of LPA receptors and function of LPA in granulosa-lutein cells. Design: Granulosa-lutein cells were obtained from women undergoing in vitro fertilization. We examined the expression of LPA receptors using RT-PCR. The effects of LPA on the expression of IL-6, IL-8, and vascular endothelial growth factor were examined. Signal pathways of LPA were delineated. The functions of secretory angiogenic factors were tested using human umbilical vein endothelial cells. Results: The LPA1, LPA2, and LPA3 receptors’ mRNA was identified in granulosa-lutein cells. LPA enhanced IL-8 and IL-6 expressions in a dose- and time-dependent manner. LPA functioned via LPA receptors, Gi protein, MAPK/ERK, p38, phosphatidylinositol 3-kinase/Akt, and nuclear factor-κB, and transactivation of epidermal growth factor receptor. LPA induced IL-8 and IL-6 through different pathways. LPA-induced IL-8 and IL-6 increased permeability of human umbilical vein endothelial cell monolayer. Conclusions: LPA induces IL-8 and IL-6 expressions through LPA receptors and nuclear factor-κB dependent pathways in granulosa-lutein cells. The LPA in preovulatory follicles may play a role in the angiogenesis of corpus luteum. Large amounts of LPA-induced IL-8 and IL-6 from multiple corpora luteae of stimulated ovaries may be one of the pathophysiological causes of ovarian hyperstimulation syndrome.

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