Extracellular vesicles derived from hypoxic HTR-8/SVneo trophoblast inhibit endothelial cell functions through the miR-150-3p /CHPF pathway

Our findings indicate that extracellular vesicles miR-150-3p derived from hypoxic trophoblasts inhibits endothelial cells proliferation, migration, and angiogenesis by modulating CHPF, illuminating a novel mechanism of hypoxic trophoblasts regulation of endothelial cells and their potential role in PE pathogenesis.

Normoxia and hypoxia were preconditioned to induce trophoblast cells-derived EVs. The effect of EVs, miRNA, target gene, and their interactions on endothelial cell proliferation, migration, and angiogenesis were determined. Quantitative analysis of miR-150-3p and CHPF were verified by qRT-PCR and western blotting. The binding relationship among EVs pathway was demonstrated by luciferase reporter assay.

Compared with 20%HTR-8-EV, 1%HTR-8-EV had a suppressive effect on proliferation, migration, and angiogenesis of endothelial cells. The results of miRNA sequencing showed the vital role of miR-150-3p in trophoblast-to-endothelium communication. 1%HTR-8-EV carrying miR-150-3p could move into endothelial cells and target chondroitin polymerizing factor (CHPF) gene. MiR-150-3p inhibited endothelial cell functions by regulating CHPF. In patient-derived placental vascular tissues, there was a similar negative correlating between miR-150-3p and CHPF.