ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2014
Ouabain inhibits placental sFlt1 production by repressing HSP27-dependent HIF-1α pathway.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 44 citations in OpenAlex.
- Transforming Preeclampsia Care: Molecular Diagnostics and Therapeutic Innovations.Journal of the American Society of Nephrology : JASN · 2026Review
- Sensational site: the sodium pump ouabain-binding site and its ligands.American journal of physiology. Cell physiology · 2024Review
- Luteolin prevents TNF-α-induced NF-κB activation and ROS production in cultured human placental explants and endothelial cells.Placenta · 2024Article
- Endogenous Digitalis-like Factors as a Key Molecule in the Pathophysiology of Pregnancy-Induced Hypertension and a Potential Therapeutic Target in Preeclampsia.International journal of molecular sciences · 2023Review
- Bioflavonoid luteolin prevents sFlt-1 release via HIF-1α inhibition in cultured human placenta.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- Understanding the Role of Chemerin in the Pathophysiology of Pre-Eclampsia.Antioxidants (Basel, Switzerland) · 2023Review
- Impaired renal reserve contributes to preeclampsia via the kynurenine and soluble fms-like tyrosine kinase 1 pathway.The Journal of clinical investigation · 2022Article
- Ferroptosis and Its Emerging Role in Pre-Eclampsia.Antioxidants (Basel, Switzerland) · 2022Review
- On the potential role of globins in brown adipose tissue: a novel conceptual model and studies in myoglobin knockout mice.American journal of physiology. Endocrinology and metabolism · 2021Article
- A Multi-Objective Approach for Drug Repurposing in Preeclampsia.Molecules (Basel, Switzerland) · 2021Article
- Potency of Tokishakuyakusan in treating preeclampsia: Drug repositioning method by in vitro screening of the Kampo library.PloS one · 2020Article
- Pre-eclampsia: pathogenesis, novel diagnostics and therapies.Nature reviews. Nephrology · 2019Review
- AP39, a Modulator of Mitochondrial Bioenergetics, Reduces Antiangiogenic Response and Oxidative Stress in Hypoxia-Exposed Trophoblasts: Relevance for Preeclampsia Pathogenesis.The American journal of pathology · 2019Article
- Taming preeclampsia at its source.Nature biotechnology · 2018Article
- Angiogenic factors: potential to change clinical practice in pre-eclampsia?BJOG : an international journal of obstetrics and gynaecology · 2018Review
- Gestational Hypoxia and Developmental Plasticity.Physiological reviews · 2018Review
- Positive and Negative Regulation of Angiogenesis by Soluble Vascular Endothelial Growth Factor Receptor-1.International journal of molecular sciences · 2018Review
- Therapeutic concentrations of digitoxin inhibit endothelial focal adhesion kinase and angiogenesis induced by different growth factors.British journal of pharmacology · 2017Article
- Cardiac glycosides suppress the maintenance of stemness and malignancy via inhibiting HIF-1α in human glioma stem cells.Oncotarget · 2017Article
- Endogenous Ouabain: Recent Advances and Controversies.Hypertension (Dallas, Tex. : 1979) · 2016Review
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Up-regulation of placental soluble fms-like tyrosine kinase 1 (sFlt1) contributes to the pathogenesis of preeclampsia. To evaluate novel upstream pathways that regulate placental sFlt1 production, we screened a library of natural compounds (n=502) in human placental cell lines. Here, we report 3 compounds in the cardiac glycoside family, ouabain, gitoxigenin, and digitoxin, that inhibit placental sFlt1 production at nanomolar concentrations in vitro. We further characterized ouabain and demonstrated that it inhibits sFlt1 mRNA and protein expression in human placental cytotrophoblasts and explant cultures in a dose- and time-dependent manner. Ouabain down-regulated sFlt1 production by inhibiting hypoxia-inducible factor 1 (HIF-1α) protein expression in the placenta. Furthermore, we found that phosphorylation of heat-shock protein 27 (HSP27) was necessary for ouabain to inhibit HIF-1α translation. In a rat model of pregnancy-induced hypertension, ouabain reduced mean arterial pressure and enhanced placental HSP27 phosphorylation without any adverse effects on pups. Further studies are needed to explore the usefulness of targeting HIF-1α/HSP27 pathway in preeclampsia.
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