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bioRxiv · 10.1101/2024.10.21.619546

hsa-miR-9-5p highly expressed in syncytiotrophoblast-derived extracellular vesicles from early-onset preeclampsia impairs cerebral microvascular endothelial cell pro-angiogenic capacity

Logenthiran, P. V.·Awoyemi, T.·Davis Jones, G.·Rahbar, M.·Akbar, N.·Cerdeira, A. S.·Escudero, C.·Vatish, M.
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Abstract

BackgroundCerebrovascular complications are the leading cause of maternal mortality associated with preeclampsia. Extracellular vesicles (EVs) containing microRNAs (miRNAs) and derived from syncytiotrophoblast (STB-EVs) are suspected to play a role in these complications. Previously, we found that STB-EVs from the placentas of women with preeclampsia have a higher content of the angiogenesis regulator hsa-miR-9-5p. We now investigate the effects of hsa-miR-9-5p on the proangiogenic properties of brain endothelial cells and identify potential protein targets involved in these processes. MethodsBrain endothelial cells (hCMEC/D3) were treated with hsa-miR-9-5p (0, 5 and 10 nM) to assess cell viability and proliferation. Additionally, cell migration and proteomic profile in hCMEC/D3 treated with hsa-miR-9-5p (10 nM) were also analyzed. ResultsCompared to control, hsa-miR-9-5p significantly reduced hCMEC/D3 cell proliferation and migration without affecting cell viability. Proteomic analysis identified several vital proteins potentially mediating these effects, including vascular endothelial growth factor type C (VEGFC), placental growth factor (PLGF or PGF), and platelet-derived growth factor B (PDGFB). Treatment with hsa-miR-9-5p did not impair the capacity of hCMEC/D3 to respond to tumour necrosis factor- (TNF-). Conclusionhsa-miR-9-5p reduces hCMEC/D3 cell proliferation and migration, and modulates the expression of angiogenic regulators such as VEGFC, PLGF, and PDGFB, without affecting TNF- mediated activation of hCMEC/D3. This suggests that STB-EVs cargo hsa-miR-9-5p may selectively inhibit the proangiogenic capacity of brain endothelial cells. These findings enhance our understanding of cerebrovascular alterations in preeclampsia and may guide future studies and therapeutic interventions.

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Logenthiran, P. V., Awoyemi, T., Davis Jones, G., Rahbar, M., Akbar, N., Cerdeira, A. S., Escudero, C., Vatish, M.. 2024-10-24. hsa-miR-9-5p highly expressed in syncytiotrophoblast-derived extracellular vesicles from early-onset preeclampsia impairs cerebral microvascular endothelial cell pro-angiogenic capacity. https://doi.org/10.1101/2024.10.21.619546

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