MicroRNA-510-3p regulated vascular dysfunction in Preeclampsia by targeting Vascular Endothelial Growth Factor A (VEGFA) and its signaling axis

Introduction: Preeclampsia (PE) is a pregnancy complication associated with multi-organ damage and vascular dysfunction. Meanwhile, microRNAs or miRNAs are crucial regulators of gene expression in various diseases including PE. Our previous studies reported high expression of miR-510 in the PE patients' blood compared to normal. Hence, we hypothesize that miR-510-3p targets Vascular endothelial growth factor A (VEGFA) in the regulation of PI3K/AKT/eNOS/mTOR axis in PE and miR-510-3p could be a potential therapeutic target for PE. Methods: The proliferation, migration, and apoptosis of HTR8/SVNeo and BeWo cells were analyzed by manipulating the miR-510-3p and VEGFA expression. Similarly, the inhibition of miR-510-3p through anti-miR510-3p was analyzed in PE rat models, and the biochemical, hemodynamic parameters, and histopathology were examined between the groups. Moreover, the expression of miR-510-3p and VEGFA/PI3K/AKT/eNOS/mTOR axis was analyzed using qRT-PCR and Western blot. Results: Significant changes were observed in the BP, proteinuria, and other biochemical parameters between PE and control rats. Our results suggest that miR-510-3p targets VEGFA leading to vascular dysfunction in PE, while treatment with anti-miR-510-3p in the PE-induced rat model exhibits a significant change in the expression of miR-510-3p/VEGFA/PI3K/AKT/eNOS/mTOR signaling where miR-510-3p showed lesser expression and vice versa with VEGFA. The gene and protein expression analysis revealed a significant correlation between miR-5103p and the VEGFA signaling axis in PE. Discussion: Thus, our findings from in vitro and in vivo suggest miR-510-3p as a potential therapeutic target and anti-miR-510-3p as a novel therapeutic molecule for PE.