# Identification and functional analysis of differential miRNAs in young and middle-aged adults with essential hypertension: exploring potential biomarkers and therapeutic targets

## TL;DR

This study identifies specific microRNAs linked to essential hypertension in young and middle-aged adults, suggesting new biomarkers and potential treatment targets.

## Contribution

The study identifies novel miRNAs and their associated proteins that may serve as biomarkers or therapeutic targets for essential hypertension.

## Key findings

- 14 upregulated and 1 downregulated miRNA were identified in essential hypertension patients.
- miRNAs were linked to pathways involving hypoxia, inflammation, vascular remodeling, and apoptosis.
- GPCPD1 was identified as a risk factor, while CDKN1B, PDGFRA, and THBS2 were protective factors for essential hypertension.

## Abstract

Essential hypertension (EH) in young and middle-aged adults is a major risk factor for cardiovascular morbidity, yet the detailed molecular mechanisms underlying this condition have not been fully understood. MicroRNAs (miRNAs) have emerged as critical regulators of gene expression and have been increasingly associated with hypertension pathogenesis.

Initially, high-throughput sequencing was employed to identify miRNAs with differential expression profiles in plasma collected from six EH patients compared with six matched healthy individuals. These candidate miRNAs were then confirmed through quantitative real-time PCR (qRT-PCR). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to elucidate the potential biological roles of these miRNAs. Mendelian randomization (MR) was subsequently applied to investigate causal associations between EH and proteins targeted by the identified miRNAs.

Differential expression analysis revealed 14 upregulated miRNAs and 1 downregulated miRNA in the EH group. Following this, miRNAs were enriched through MiEAA, resulting in the selection of one downregulated miRNA and four upregulated miRNAs, which were subsequently validated by qRT-PCR. KEGG pathway analysis showed that genes regulated by upregulated miRNAs were significantly enriched in pathways related to hypoxia (HIF-1 signaling pathway), inflammation (MAPK and JAK-STAT signaling pathways), vascular remodeling (Focal adhesion and TGF-beta signaling pathways), and apoptosis (p53 signaling pathway). MR analysis identified GPCPD1, regulated by hsa-miR-10b-5p, as a significant risk factor for EH (OR = 1.04, 95% CI: 1.00–1.09, p = 2.32 × 10−3). Moreover, proteins regulated by upregulated miRNAs, such as CDKN1B, PDGFRA, and THBS2, were found to be protective factors against EH.

GPCPD1, regulated by hsa-miR-10b-5p, is a potential risk factor for EH, while CDKN1B, PDGFRA, and THBS2, regulated by upregulated miRNAs, may act as protective factors. These findings suggest new biomarkers and therapeutic targets for hypertension.