Regulatory Role of miR-196a-5p in Angiogenesis-Related Markers in Endothelial Cells Exposed to Hypertensive Pregnancies

Offspring of hypertensive disorders of pregnancies (HDP) exhibit early-life endothelial dysfunction and have an elevated susceptibility to hypertension during adulthood which is potentially mediated by microRNA (miRNA), a key regulator of gene expression. RNA sequencing showed that miR-196a-5p was significantly upregulated in HUVEC exposed to HDP and may regulate angiogenesis in endothelial cells. Therefore, this study aims to elucidate the role of miR-196a-5p in regulating angiogenesis in HUVEC exposed to HDP. miR-196a-5p expression was validated by stem-loop RT-qPCR. Predicted target genes were identified using four algorithms, miRWalk, miRDB, TargetScan, and DIANA-microT-CDS, focusing on angiogenesis-related genes. Protein expression was confirmed through ELISA. Stem-loop RT-qPCR showed that miR-196a-5p expression was significantly upregulated in HDP HUVEC. Bioinformatic analysis revealed that the <i>PDGFRA</i> gene, a key regulator for angiogenesis, was significantly enriched. Overexpression of miR-196a-5p significantly downregulated <i>PDGFRA</i>, <i>VEGF</i>, and <i>bFGF</i> in HDP HUVEC, whereas its suppression upregulated these genes significantly. The ELISA result confirmed the corresponding changes at the protein level. However, <i>PDGFRA</i> protein levels increased with miR-196a-5p overexpression and decreased with its inhibition. Collectively, the results indicate that miR-196a-5p may have a regulatory effect on <i>PDGFRA</i>, <i>VEGF</i>, and <i>bFGF</i> that is associated with angiogenesis, and the modifications could be beneficial in future epigenetic targeted therapy.