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Specific HIF-2α (Hypoxia-Inducible Factor-2) Inhibitor PT2385 Mitigates Placental Dysfunction In Vitro and in a Rat Model of Preeclampsia (RUPP).

par Colson, A.;Depoix, Christophe Louis;Lambert, Isaline ;Leducq, Camille;Bedin, Marie;De Beukelaer, M;Gatto, Laurent ;Loriot, Axelle;Peers de Nieuwburgh, Maureen;Bouhna, Khadija;Baldin, Paméla;Hubinont, Corinne ;Sonveaux, Pierre;Debieve, Frédéric
Référence Hypertension, 80, 5, page (1011-1023)
Publication Publié, 2023-05-01

Article révisé par les pairs

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Résumé :

Preeclampsia is one of the leading causes of maternal mortality worldwide and is strongly associated with long-term morbidity in mothers and newborns. Referred to as one of the deep placentation disorders, insufficient remodeling of the spiral arteries during the first trimester remains a major cause of placental dysfunction. Persisting pulsatile uterine blood flow causes abnormal ischemia/reoxygenation phenomenon in the placenta and stabilizes the HIF-2α (hypoxia-inducible factor-2α) in the cytotrophoblasts. HIF-2α signaling impairs trophoblast differentiation and increases sFLT-1 (soluble fms-like tyrosine kinase-1) secretion, which reduces fetal growth and causes maternal symptoms. This study aims to evaluate the benefits of using PT2385-an oral specific HIF-2α inhibitor-to treat severe placental dysfunction.