Serum exosomal miRNA signature in hypertension: an exploratory study integrating with comparative analysis of the GEO database.

Abstract

Essential hypertension (EH) remains a leading cause of mortality worldwide. Exosome-carried microRNAs (miRNAs) play a pivotal role in the pathogenesis of EH. In this exploratory study, we aimed to characterize the serum exosomal miRNA expression profile in patients with EH and to investigate the potential functional relevance of differentially expressed (DE) miRNAs, aiming to provide preliminary evidence for future mechanistic investigations. Serum exosomes were isolated from patients with EH and healthy controls, followed by small RNA sequencing. Differentially expressed (DE) miRNAs were identified and further subjected to bioinformatic target gene prediction. To elucidate the potential biological functions of these target genes, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Additionally, a comparative analysis of the DE miRNAs was conducted using an independent dataset from the Gene Expression Omnibus (GEO) database. Six significantly downregulated miRNAs (hsa-miR-16-5p, hsa-miR-652-3p, hsa-miR-93-5p, hsa-miR-17-5p, hsa-miR-20a-5p, hsa-miR-193a-5p) were identified in 20 hypertensive patients compared with 10 healthy controls. GO and KEGG analyses revealed that the predicted target genes of these miRNAs were significantly enriched in biological processes related to neuronal function, protein homeostasis, and cell cycle regulation, and were primarily involved in MAPK, Hippo, p53, and TGF-β signaling pathways. Notably, comparative analysis of the GEO dataset demonstrated a distinct expression profile between exosomal and total plasma miRNAs, underscoring the unique value of exosome-specific analysis. This exploratory study identified six serum exosomal miRNAs as candidate biomarkers for hypertension, with predicted targets enriched in MAPK and TGF‑β pathways. The exosomal signature was distinct from total plasma miRNA profiles, suggesting that exosomal miRNAs may carry disease‑specific signals. However, given the limited sample size and exploratory nature of this study, these findings are preliminary and require validation in larger cohorts.