Serum from patients with hypertension promotes endothelial dysfunction to induce trophoblast invasion through the miR-27b-3p/ATPase plasma membrane Ca2+ transporting 1 axis.

Pregnancy-induced hypertension is often accompanied by preeclampsia. The present study investigated whether microRNA (miR)-27b-3p affected the occurrence of preeclampsia by regulating the function of endothelial cells. Expressions levels of miR-27b-3p and ATPase plasma membrane Ca2+ transporting 1 (ATP2B1) were determined using reverse-transcription quantitative PCR. miR-27b-3p targeting ATP2B1 was predicted using bioinformatics and further confirmed by dual-luciferase reporter assays. Cell Counting Kit-8, Transwell and Matrigel tube formation assays were performed to detect the effects of miR-27b-3p on proliferation, migration and tube formation of human umbilical vein endothelial cells (HUVECs), respectively. Moreover, HTR8/SVneos cells were co-cultured with HUVECs to detect the invasion of trophoblast cells, and the expression levels of vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2 and MMP-9 of HUVECs and HTR8/SVneos were detected by western blotting. Expression levels of miR-27b-3p were upregulated in the serum of patients with hypertension and preeclampsia, which could target and regulate the expression of ATP2B1. The expression levels of miR-27b-3p were increased and those of ATP2B1 were reduced in HUVECs from hypertensive serums. Moreover, miR-27b-3p mimics reduced the expression level of ATP2B1, and miR-27b-3p inhibitor reversed the effect of hypertensive serum on ATP2B1 expression. Furthermore, patients with hypertension showed increased endothelial dysfunction, reduced trophoblastic invasion and the expressions of VEGF, MMP-2 and MMP-9, and miR-27b-3p mimics and silencing of ATP2B1 produced similar results to HUVECs. The miR-27b-3p inhibitor reversed the effect of hypertensive serum, and silencing of ATP2B1 inhibited the improvement of miR-27b-3p inhibitor to HUVECs and HTR-8/SVneo cells in proliferation, migration and tube formation. The current findings suggested that miR-27b-3p promoted proliferation, migration and tube formation of HUVECs and enhanced invasion of trophoblast cells, via regulation of ATP2B1. Thus, miR-27b-3p could be considered as a molecular risk factor in the pathogenesis and development of preeclampsia. [ABSTRACT FROM AUTHOR]