Emerging exosomal biomarkers for essential hypertension: a systematic review.

Abstract

Background: Exosomes show promise as biomarkers for essential hypertension (EH) progression and complications. However, existing studies on dysregulation of exosomal biomarkers in hypertension lack consistency. Thus, we conducted a comprehensive systematic review to synthesize evidence on exosomal biomarkers associated with EH.

Methods: We performed an exhaustive search across PubMed, Embase, Web of Science, the Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, and Chinese Clinical Trial Registry. Our search encompassed all available Chinese and English records from their inception through August 14^th, 2025, without any restrictions on study design. The primary outcome focused on exosomal microRNA (miRNA) alterations, with secondary analyses of other cargo types (e.g., proteins). We employed the Joanna Briggs Institute (JBI) critical appraisal tool and the risk of bias in non-randomized studies of interventions (ROBINS-I) tool to assess the risk of bias. Due to the limitations of the data in the included studies, we conducted a qualitative narrative synthesis to summarize key study characteristics and synthesize their principal findings. The protocol was prospectively registered on PROSPERO (CRD42023470885).

Results: The qualitative analysis included 11 identified studies, which revealed moderate-to-high methodological quality (JBI: 6 moderate, 4 high), with one study exhibiting a moderate risk of bias (ROBINS-I). This systematic review revealed that exosomal biomarkers in blood and urine had diagnostic potential for hypertension and its complications. Evidence suggested that exosomal biomarkers were associated with hypertensive vascular dysfunction (e.g., increased miR-320d/423-5p) and may provide a molecular basis for precise typing of hypertension (platelet-derived extracellular vesicles). Notably, exosomal biomarkers may serve as indicators of target organ damage, reflecting early renal injury (decreased miR-26a-5p) and cognitive dysfunction (decreased miR-330-3p) in hypertension.

Conclusions: This systematic review highlights the value of blood and urine exosomal biomarkers in the early diagnosis, precise typing, and monitoring of target organ damage in hypertension and its complications. Future studies should systematically compare exosomal biomarkers with conventional markers using standardized protocols. Methodological improvements should focus on expanding larger sample sizes, enhancing reporting completeness and transparency, and standardizing data-sharing practices.