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.

microRNA‑27b‑3p; ATPase plasma membrane Ca2+ transporting 1; HUVECs; hypertension; preeclampsia.