SFEBES2023 Poster Presentations Reproductive Endocrinology (42 abstracts)
Immunometric and functional measurement of endogenous vasoinhibin in human sera
Magdalena Zamora 1,2 , David Harris 1 , Nils Davies 1 , Johannes Ebnet 1 , Peter Radermacher 3 , Cosima Brucker 1 , Christiane Waller 1 , Juan Pablo Robles 2 , Thomas Bertsch 1 , Carmen Clapp 2 & Jakob Triebel 1
1Nuremberg General Hospital & Paracelsus Medical University, Nuremberg, Germany. 2Universidad Nacional Autónoma de México (UNAM), Querétaro, Mexico. 3University of Ulm, Ulm, Germany
Circulating levels of the antiangiogenic protein vasoinhibin (16 kDa PRL), a fragment of prolactin, are of interest in vasoproliferative retinopathies, preeclampsia, and peripartum cardiomyopathy, but are unknown due to the lack of a quantitative assay. Here, human serum samples were investigated for the concentration and bioactivity of vasoinhibin using a novel enzyme-linked immunosorbent assay (ELISA) for human vasoinhibin employing an anti-vasoinhibin monoclonal antibody, a human umbilical vein endothelial cells (HUVEC) proliferation assay and a chick chorioallantoic membrane (CAM) angiogenesis assay. Serum samples from 17 pregnant women with and without preeclampsia and pregnancy induced hypertension demonstrated endogenous vasoinhibin concentrations in the range between 5 and 340 ng/ml. Vasoinhibin levels were significantly higher in preeclampsia serum compared to healthy pregnancy serum (mean 63.09 vs. 19.67 ng/ml, P=0.0003), as was the bioactivity of vasoinhibin determined by HUVEC proliferation (56.12 vs. 13.38 ng/ml, P=<0.0001). There was a correlation between the concentrations of vasoinhibin measured by ELISA and by HUVEC proliferation (Pearson r=0.95, P=<0.0001). Healthy serum demonstrated a proangiogenic effect in the CAM assay (P=<0.05, compared to a PBS control), while serum from preeclamptic patients demonstrated an antiangiogenic action (P=<0.05 vs. PBS control), as did recombinant human vasoinhibin and a synthetic circular retro-inverse vasoinhibin analog (CRIVi45-51). The antiangiogenic effects in the CAM assay and the inhibition of HUVEC proliferation were abolished by the addition of the ELISA anti-vasoinhibin monoclonal antibody but not by mouse IgG. These results demonstrate the first quantitation of endogenous, bioactive vasoinhibin in human sera and its elevated levels and antiangiogenic activity in sera from women with preeclampsia. The development and implementation of a quantitative assay for vasoinhibin overcomes a long-standing barrier and opens the perspective to a thorough clinical verification of vasoinhibin as a relevant biomarker.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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