Abstract 11411: Anti-MiR-510-3p Alleviates Endothelial Dysfunction in Preeclampsia Induced Rat Model B\by Regulating PTEN and Its Signalling Pathways

Abstract

Introduction: Preeclampsia (PE) is a pregnancy complication associated with multi-organ endothelial dysfunction. The hypoxia resulting from vascular remodelling lowers blood flow in placenta leading to high mortality and morbidity in PE. Studies on molecular and signalling pathways involved in PE could pave way for early diagnosis and treatment. miRNAs are crucial regulators of gene expression in various diseases including PE. Our previous studies reported high expression of miR-510 in PE patients compared to normal. Hypothesis: We hypothesize that miR-510-3p targets PTEN in regulation of PI3K/AKT/eNOS/mTOR axis in PE and miR-510-3p could be a potential biomarker and therapeutic target. We elucidate the therapeutic role of antimiR-510-3p in PE and its interaction with miR-510-3p and associated signalling pathways in PE induced rat model. Methodology: The proliferation, migration, invasion and apoptosis of HTR/SVNeo cells were analyzed for miR-510-3p, PTEN and antimiR-510-3p. Luciferase assay confirmed PTEN as target for miR-510-3p. The expression of miR-510-3p and PTEN/PI3K/AKT/eNOS/mTOR axis was analysed using qPCR and western blot. Deoxycorticosterone (DOCA) (12.5 mg/kg before mating and 6.5 mg/kg after mating twice a week) and 0.9% salt ad libitum were used to develop a PE induced rat model (SD rats). By quantifying miR-510-3p levels in PE group, the doses of antimiR-510-3p for the dose-dependent study were determined. The final effective dose was fixed from the dose-response curve. To examine the hypoxia and hypertrophy, histological analysis was performed in paraformaldehyde fixed tissues. 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 PTEN leading to endothelial dysfunction, hypoxia and hypertrophy in PE, while treatment with antimiR-510-3p exhibits a significant reduction in PE in PE induced rat model. The gene and protein expression analysis revealed a significant correlation between miR-510-3p, PTEN and antimiR-510-3p in PE. Conclusion: Thus our findings from in vitro and in vivo suggest miR-510-3p as a potential biomarker and therapeutic target and antimiR-510-3p as a novel therapeutic molecule for PE.