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Preeclamptic plasma stimulates the expression of miRNAs, leading to a decrease in endothelin-1 production in endothelial cells

2018; Elsevier BV; Volume: 12; Linguagem: Inglês

10.1016/j.preghy.2018.03.001

2210-7797

Mayara Caldeira-Dias, Marcelo R. Luizon, Elenice Deffune, José E. Tanus‐Santos, Paula Paccielli Freire, Robson Francisco Carvalho, Heloísa Bettiol, Viviane Cunha Cardoso, Marco Antônio Barbieri, Ricardo de Carvalho Cavalli, Valéria C. Sandrim,

MicroRNA in disease regulation

Preeclampsia is a major cause of maternal and fetal morbidity and mortality worldwide. It is a multisystem pregnancy syndrome characterized by general endothelial dysfunction caused mainly by plasma factors and debris in endothelial cells. It is widely accepted that endothelin-1 (ET-1) is involved in the pathophysiology of preeclampsia, and so it is of interest to ascertain whether the ET-1 gene (EDN1) can be targeted with tools such as miRNAs. Therefore, we investigated the relationship between the expression of miRNAs that putatively target EDN1 (and so affect ET-1 levels) in HUVECs incubated with plasma from preeclamptic women. EDN1 expression and ET-1 levels in HUVECs incubated with plasma from women with preeclampsia were similar to those in plasma from healthy pregnant women. Expression of miRNAs let-7a, -7b, and -7c, and to a lesser degree 125a and 125b, was increased in preeclampsia. Expression of miRNAs of the let-7 family was significantly negatively correlated with ET-1 levels in preeclampsia. Transfection of the preeclampsia cultures with mimic miRNA let-7 decreased ET-1 levels. Our findings show that preeclamptic plasma stimulates the expression of miRNAs in HUVECs, leading to a decrease in ET-1levels, which suggests that therapeutic miRNAs may aid in the management of preeclampsia.