Identification of an Exosomal miRNA Signature in Newly Diagnosed Essential Hypertensive Adults

Abstract

Background: Hypertension is a major risk factor for cardiovascular diseases and premature death worldwide. Less than half of adults with hypertension are not properly diagnosed and treated indicating a need for better diagnostic and treatment strategies. Exosomal miRNAs have been implicated in hypertension development and show potential as non-invasive disease biomarkers. Therefore, this study aimed to investigate potential exosomal miRNA biomarkers of hypertension to enhance early detection. Methods: Plasma exosomes from newly identified, stage I essential hypertensive adults and their controls were isolated and characterised. The miRNA profiles were compared using small RNA sequencing, then validated with quantitative PCR (qPCR). Enriched pathways and gene ontologies of predicted miRNA targets were compared against systemically dysregulated pathways to validate its biological function. Results: Hypertensives showed preferential release of exosomes larger than 150 and significantly reduced expression of exosomal CD9. After qPCR validation, a unique hypertensive exosomal miRNA profile consisting of three downregulated and one upregulated miRNA was identified. The combination of this miRNA signature (hsa-miR-184, hsa-miR-432-5p, hsa-miR-1-3p, and hsa-miR-1246) with BMI demonstrated the highest diagnostic value. Predicted target pathways of the miRNA signature and systemically dysregulated proteomics pathways highlighted the convergence of aberrant metabolic pathways in the development of hypertension. Conclusion: This study identified a unique hypertensive exosomal miRNA profile when used combination with BMI. The miRNA signature provided insights into the mechanisms involved in the early stages of hypertension and offers leads for further validation in biomarker discovery to alleviate the burden of cardiovascular diseases.