Development and repurposing of
therapies that show promise in the prevention or treatment of
preeclampsia would be a major advance for the obstetrics field. We recently identified
esomeprazole and
sulfasalazine as potential candidates for the treatment of
preeclampsia. Both reduce placental and endothelial secretion of sFlt-1 and sENG and mitigate endothelial dysfunction in vitro. Here we assessed whether
esomeprazole and
sulfasalazine in combination would additively attenuate the elevated release of anti-angiogenic factors and markers of endothelial dysfunction, key characteristics of
preeclampsia. Primary placental tissue and cells, and primary endothelial cells were treated with
esomeprazole and
sulfasalazine alone and in combination. We assessed secretion of sFlt-1 and sENG and performed in vitro assays of endothelial dysfunction. Combining
esomeprazole and
sulfasalazine in lower concentrations caused an additive reduction in sFlt-1 secretion in primary cytotrophoblasts, placental explants and endothelial cells. No additive reduction was observed in sENG secretion when
esomeprazole and
sulfasalazine were combined. Together,
esomeprazole and
sulfasalazine additively reduced TNF-α-induced VCAM and ET-1
mRNA expression, and monocyte adhesion to endothelial cells. In conclusion, combining
esomeprazole and
sulfasalazine additively reduced secretion of sFlt-1 and markers of endothelial dysfunction. Combined administration of
esomeprazole and
sulfasalazine may provide a more effective treatment or prevention for
preeclampsia compared to either as single agents.