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

TL;DR

This study shows that miR-196a-5p affects angiogenesis-related genes in endothelial cells from pregnancies with hypertension, suggesting a potential role in future therapies.

Contribution

The study identifies miR-196a-5p as a novel regulator of PDGFRA, VEGF, and bFGF in endothelial cells under hypertensive pregnancy conditions.

Findings

miR-196a-5p is significantly upregulated in HUVEC exposed to HDP.

Overexpression of miR-196a-5p downregulates PDGFRA, VEGF, and bFGF at the mRNA level.

PDGFRA protein levels increase with miR-196a-5p overexpression and decrease with its inhibition.

Abstract

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 PDGFRA gene, a key regulator for angiogenesis, was significantly enriched. Overexpression of miR-196a-5p significantly downregulated PDGFRA, VEGF, and bFGF in HDP HUVEC, whereas its suppression upregulated these genes significantly. The ELISA result confirmed the corresponding changes at the protein level. However, PDGFRA 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 PDGFRA, VEGF, and bFGF that is associated with angiogenesis, and the modifications could be beneficial in future epigenetic targeted therapy.

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