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

  • Placenta. 2023 Jul:138:21-32. doi: 10.1016/j.placenta.2023.04.017.
Menghan Sha  1 ,  Shunran Zhang  2 ,  Rajluxmee Beejadhursing  2 ,  Yanan Sun  2 ,  Yu Qin  2 ,  Suhua Chen  3 ,  Wei Li  2
Affiliations
  • 1. Department of Obstetrics and Gynecology, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, China. Electronic address: [email protected].
  • 2. Department of Obstetrics and Gynecology, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, China.
  • 3. Department of Obstetrics and Gynecology, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, China. Electronic address: [email protected].
PMID: 37156185 DOI: 10.1016/j.placenta.2023.04.017
Abstract

Introduction: Endothelial dysfunction is one of the basic pathological changes in pre-eclampsia. Extracellular vesicles (EVs) can transport miRNAs expressed by placental trophoblast cells into endothelial cells. The aim of this study was to explore the differential effects of EVs induced by hypoxic trophoblasts (1%HTR-8-EV) and those derived from normoxic trophoblasts (20%HTR-8-EV) on the regulation of endothelial cell functions.

Methods: 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.

Results: 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.

Discussion: 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.

Keywords
Endothelial cell; Extracellular vesicle; miR-150-3p.
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