Combining metformin and esomeprazole is additive in reducing sFlt-1 secretion and decreasing endothelial dysfunction - implications for treating preeclampsia

PloS One
T J Kaitu'u-LinoNatalie J Hannan

Abstract

The discovery of new treatments that prevent or treat preeclampsia would be a major advance. Antiangiogenic factors soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sENG) are secreted in excess from the placenta, causing hypertension, endothelial dysfunction, and multiorgan injury. We recently identified metformin and esomeprazole as potential treatments for preeclampsia. Both reduce placental and endothelial secretion of sFlt-1 and soluble endoglin, and reduce endothelial dysfunction. We set out to assess whether combining metformin and esomeprazole would additively reduce sFlt-1 and soluble endoglin secretion and reduce endothelial dysfunction (verses drug alone). Metformin and esomeprazole were added to primary placental cells and tissues, and endothelial cells and their effects on sFlt-1 and soluble endoglin secretion were assessed in vitro. Tumor necrosis factor-α (TNF-α) was added to endothelial cells to induce dysfunction in vitro. We examined the ability of metformin + esomeprazole to rescue TNF-α induced vascular cell adhesion molecule-1 (VCAM-1) and Endothelin-1 (ET-1) expression, leukocyte adhesion (markers of endothelial dysfunction). Combining metformin and esomeprazole was additive at reducing sFl...Continue Reading

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Citations

Mar 5, 2019·Hypertension·Roxanne HastieSusanne Hesselman
Mar 29, 2019·Circulation Research·Sarosh RanaS Ananth Karumanchi
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Jan 20, 2019·Scientific Reports·Carole-Anne WhighamTu'uhevaha J Kaitu'u-Lino
Apr 4, 2021·Antioxidants·Annie Langston-CoxEuan M Wallace
Jul 3, 2021·Journal of Clinical Medicine·Elżbieta Poniedziałek-CzajkowskaBożena Leszczyńska-Gorzelak
Aug 8, 2021·Journal of Clinical Medicine·Natalie K BinderNatalie J Hannan
Jul 2, 2021·Molecular and Cellular Biochemistry·Lissette Sanchez-Aranguren, Sarah Nadeem
Jul 4, 2020·American Journal of Perinatology·Natalie A BelloAlexander M Friedman

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