Emerging exosomal biomarkers for essential hypertension: a systematic review

Introduction

Hypertension accounts for 8.5 million of the global deaths related to stroke, ischemic heart disease, and various vascular diseases (1,2). Between 1990 and 2019, the number of patients with hypertension aged 30–79 years rose significantly, from 331 million women and 317 million men to 626 million women and 652 million men, respectively (3). The healthcare expenditure of hypertension leverages a heavy burden on families, health systems and societies. Consequently, hypertension has become the most significant contributor to the global disease burden, and thus greater attention should be paid to this issue. Essential hypertension (EH), involving the interplay of genetic, epigenetic, and environmental factors, accounts for 95% of all the patients with hypertension (4). Current hypertension diagnosis and treatment decisions depend on blood pressure (BP) measurements. BP is the most important treatment monitoring tool to help estimate risk of hypertension-related organ damage. However, BP measurements cannot distinguish subtypes or reveal underlying mechanisms and may not be the best tool to monitor therapeutic success (5,6). Although BP measurements maintain its fundamental role in clinical practice, its integration with mechanistically informative biomarkers is beneficial for early intervention, biomarker-guided therapy may both prevent BP-related complications and guide the development of novel antihypertensive regimens (6).

Exosomes are nanoscale membrane-encapsulated extracellular vesicles (EVs) that range from 30 to 120 nanometers in size. Exosomes play a crucial role in cell-to-cell communication by transporting various cargo, including RNA, proteins, lipids, and other elements, from the parent cell to the recipient cell (7-9).

Exosomes mediate critical physiological processes including intercellular communication and angiogenesis, positioning them as promising diagnostic biomarkers for various diseases (10). Evidence indicates that exosomal microRNAs (miRNAs) contribute to the pathophysiological processes of hypertension, making them promising therapeutic and diagnostic markers for hypertension (11-13). Beyond miRNAs, research suggests that exosomes contain a key receptor, angiotensin II type I receptor (AT1R), which is critical to cardiovascular function. Under conditions of in vivo cellular stress, the heart releases exosomes enriched with AT1R, potentially modulating vascular responses to neurohormonal stimulation (14). Vascular smooth muscle cells (VSMCs) are essential to the regulation of vascular calcification, and nearly all individuals with cardiovascular disease have certain degree of calcification (15). A previous study demonstrated that endoplasmic reticulum stress could mediate VSMC calcification via increasing the release of glucose-regulated protein 78 kDa (Gpr78)-loaded EVs (16).

The literature on exosomes and hypertension is growing. However, the EH related exosomal biomarkers identified by various studies are inconsistent (10-13). Although a single study has explored the broader role of miRNAs in hypertension and coronary artery disease (17), no investigations have specifically addressed exosomal cargo in hypertension. Therefore, we conducted a comprehensive overview of the types and sources of exosomal cargo that distinguished patients with hypertension from healthy individuals, with the aim of establishing a foundation for the development of exosomal biomarker-based approaches for hypertension and its complications. We present this article in accordance with the PRISMA reporting checklist (available at https://cdt.amegroups.com/article/view/10.21037/cdt-2025-76/rc) (18).

Methods

The study protocol of this systematic review has been registered on PROSPERO (registration ID: CRD42023470885).

Search strategy

We conducted a comprehensive search of electronic databases, including PubMed, Embase, Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang Database, from their inception to August 14^th, 2025. We employed broad search strategies tailored to each database’s retrieval rules, using keywords such as “exosome” and “hypertension” (see Appendix 1 for details). Additionally, we manually searched reference lists and gray literature (Chinese Clinical Trial Registry) for possible studies.

Selection criteria

We included studies meeting the following criteria: (I) adult patients (over 18 years of age) with EH (diagnosed using recognized diagnostic criteria) and healthy individuals; (II) an exposure consisted of patients with EH and dysregulation of exosomal cargo; (III) a comparator was healthy individuals with exosomal cargo; and (IV) outcomes included exosomal cargo obtained from blood, urine, or saliva. The concentration of miRNA was taken as the primary outcome and other target outcomes involved exosomal cargo such as proteins, lipids, messenger RNA, and circular RNA.

We excluded the following literature: (I) reviews, commentaries, letters, case reports, or conference abstracts; (II) studies in which data were not available or accessible; (III) duplicate publications; and (IV) studies published in languages other than Chinese and English. For studies with overlapping populations, we prioritized the study with the largest sample size or selected the most comprehensive exosomal analysis when sample sizes were similar.

Study selection

Retrieved studies were imported into the EndNote software (Clarivate Analytics, London, UK) for removal of duplicates. Two researchers (D.Z. and Y.Z.) screened the titles and abstracts based on the eligible criteria. Subsequently, the full texts of the selected studies were downloaded for further evaluation. To ensure accuracy, the included studies were cross-checked by two researchers (D.Z. and Y.Z.), and a third researcher (J.L.) was consulted to resolve any disagreements.

Data extraction

Two independent reviewers (Y.C. and Q.L.) extracted data with a predefined data extraction form. The extracted data comprised study characteristics (first author, publication year, country, and study type), participant details (sample size, gender, age, and diagnostic criteria), exosome parameters (types, sources, and isolation methods), information on risk of bias and key conclusions. We contacted corresponding authors for any missing information. Extracted information was cross-checked, and disagreements were resolved by team discussion.

Risk of bias assessment

We employed the Joanna Briggs Institute (JBI) critical appraisal tool (available at https://jbi.global/critical-appraisal-tools) with design-specific adaptations. For hybrid designs [e.g., randomized controlled trials (RCTs) with reference cohorts], only the reference cohort components were evaluated. The checklist consists of 8 items, with responses including ‘Yes’, ‘No’, ‘Unclear’, or ‘Not applicable’. Total scores were interpreted as follows: 1–3 (low quality), 4–6 (moderate quality), and 7–8 (high quality). The risk of bias of non-randomized intervention studies was rigorously evaluated using the risk of bias in non-randomized studies of interventions (ROBINS-I) tool (19). This tool evaluates studies across seven domains. Each study was judged to have ‘low’, ‘moderate’, ‘serious’, or ‘critical’ risk of bias for each domain. Any discrepancy was arbitrated by a senior reviewer (R.J.).

Summary of findings

Due to the data constrained in the included studies, we were unable to perform a conventional meta-analysis with pooled effect size estimation. Descriptive and qualitative analyses were performed to summarize the study results. First, we conducted narrative analyses for all included studies with summary of sample sizes, study designs, key variables, measurement methods and the key findings from each study. Additionally, we focused on the limitations and uncertainties of the conclusions obtained.

Results

Search results

As shown in Figure 1, a total of 3,700 possibly relevant publications were initially identified. After removing 889 duplicates, we further screened 2,811 publications. Following a review of the titles and abstracts, 829 articles were then excluded. Finally, 11 eligible publications (represented by 11 reports) were included after the complete texts of 1,982 research articles were examined (12,20-29). To ensure comprehensive coverage, we performed manual reference checking of all citations (n=815) from these 11 included studies. However, no new eligible studies were included.

Figure 1 PRISMA flowchart. CNKI, China National Knowledge Infrastructure; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Study characteristics

Ultimately, 11 studies were included in this systematic review (12,20-29), involving 541 hypertensive patients and 173 healthy controls, with individual study sample sizes ranging from 3 to 86 participants per group. Table 1 summarizes the characteristics of the included studies: all eligible studies were conducted between 2014 and 2024. Six studies were conducted in China, one in Australia (21), one in America (24), two in Spain (12,23), and one in Denmark (20). The included studies comprised two randomized intervention studies with reference cohorts (26,29), one non-randomized intervention study (20), one translational study with reference cohort (25), and seven observational studies (12,21-24,27,28). Among these, three studies extracted exosomes from plasma (21,25,27), two from serum (22,26), five from urine (12,20,24,28,29), and one from both plasma and urine (23). Moreover, seven studies focused on exosomal miRNAs (12,22,23,25-27,29).

Risk of bias assessment

Table 2 shows the assessment of risk of bias (see Tables S1,S2 for details). The results of risk of bias assessment revealed that most studies inadequately controlled for confounding factors, particularly antihypertensive medication use (20,25-29). In summary, six studies (21,25-29) were rated as moderate quality and four (21-24) as high quality via JBI criteria. One study (20) showed a moderate risk of bias via ROBINS-I.

Potential exosomal biomarkers in blood

Table 3 displays the top 10 most significantly up/down-regulated exosomal biomarkers presented in the blood of hypertensive patients (see Tables S3,S4 for the full exosome data). Lugo-Gavidia et al. found that there was a significant association between circulating platelet-derived EVs and nocturnal BP, dipping status, and pulse wave velocity (PWV), which suggested that EVs could serve as a potential early biomarker for underlying vascular health status. Besides, when comparing different hypertensive phenotypes, EV levels were lower in the white coat hypertension compared to sustained hypertension (21). Other studies demonstrated that multiple exosomal miRNAs of plasma and serum in patients with EH differed significantly from healthy volunteers (22,23,25-27). Among the various EV-miRNAs, miRNAs such as miR-320d and miR-423-5p were found to be involved in the pathophysiological processes of EH. In spontaneously hypertensive rats, therapeutic delivery of miR-320d/423-5p inhibitors via engineered EV could alleviate the phenotype, and miR-320d/423-5p had the potential to be the therapeutic target for hypertension associated vascular disease (25). Notably, although one study reported distinct miRNA expression patterns across ethnic groups with hypertension, the limited sample sizes in each subgroup compromised the statistical power to establish robust ethnicity-specific profile (27). This finding underscores the potential influence of genetic and environmental factors on miRNA expression in hypertensive patients. Additionally, miRNAs may be linked to complications of elevated BP, particularly in cognitive impairment and albuminuria. Ma et al. found that decreased expression of miRNA-330-3p might contribute to cognitive impairment in patients with hypertension by decreasing frontal cerebrovascular reactivity and could be a biomarker of early diagnosis for hypertension-associated cognitive decline (22). Perez-Hernandez et al. revealed that miR-126-3p and miR-26a-5p levels in plasma exosomes of patients with hypertension without persistent elevated urinary albumin excretion (UAE) were significantly different from healthy individuals. In particular, exosomes miR-26a were reported to play a key role in the regulation of transforming growth factor-β (TGF-β), which is a relevant effector in podocyte damage (23).

Potential exosomal biomarkers in urine

Table 4 summarizes the exosomal biomarkers presented in the urine of hypertensive patients. Song found that compared with healthy controls, 88 upregulated proteins [including Na-Cl cotransporter (NCC) and proteins] and 66 downregulated proteins were detected in the urinary exosomal composition of patients with hypertension (28). Compared with non-UAE and UAE patients, the miR-26a-5p levels both in urine and plasma exosomes were significantly elevated in healthy populations, suggesting that exosomal miRNAs may serve as biomarkers of early kidney damage in hypertension (23). Subsequent work by Perez-Hernandez et al. indicated that exosome miR-146a level was inversely associated with albuminuria and discriminated the presence of urinary albumin excretion [area under the curve (AUC) =0.80, 95% confidence interval: 0.66–0.95; P=0.0013] (12). Moreover, Zhang also revealed that patients with hypertension and early renal damage exhibited notably decreased levels of miR-200a-3p and miR-29a-5p mRNA transcripts in contrast to healthy individuals (29). Additionally, the percentage of urinary p16⁺ EVs, as well as those coexpressing p16⁺ with urate transporter 1 or prominin-2, was higher in patients with hypertension than that in healthy controls (24). One study documented that patients with hypertension had a lower expression of retinoic acid-induced gene 2 protein (RAIG-2) and syntenin-1 in comparison to healthy controls (20).

Discussion

The current systematic review included 11 qualified studies involving a total of 541 hypertensive cases and 173 normotensive controls, where the sample size of individual studies ranged from 3 to 86 participants per arm. Exosomal biomarkers in both blood and urine exhibited diagnostic potential for hypertension and its complications. Notably, exosomal signatures may serve as indicators for detection and treatment of target organ damage in hypertension. Furthermore, exosomal biomarkers may be the molecular basis for precise typing of hypertension.

Current evidence highlighted the critical role of exosomes in mediating vascular dysfunction in hypertension through multiple mechanisms. Lugo-Gavidia et al. demonstrated that circulating platelet-derived EVs correlated with nocturnal BP, dipping, and PWV, which is a well-established marker of arterial stiffness and a strong predictor of cardiovascular events (21). These findings positioned platelet-derived EVs as promising integrative biomarkers of vascular health, particularly given the established association between elevated nocturnal BP and progressive vascular organ damage (30,31). Beyond their diagnostic potential, exosomes serve as natural carriers of miRNAs, providing exceptional stability in circulation and facilitating intercellular communication (32). Wang et al. revealed that the EVs from the injured endothelial cells could remodel the vessel wall in hypertension via switching the smooth muscle cells (SMCs) phenotype with miR-320d and miR-423-5p (25). Both miR-320d and miR-423-5p have been previously implicated in SMC phenotypic switching and functional regulation, as evidenced by prior mechanistic studies (33-35). Notably, therapeutic delivery of miR-320d/423-5p inhibitors via engineered EVs alleviated the phenotype in spontaneously hypertensive rats, which shed light on therapeutic intervention of arterial stiffening (25). Complementing these findings, Ren et al. identified age-dependent alterations in cardioprotective exosomal miRNAs that inversely correlated with progressive vascular stiffness and hypertension development (36). Collectively, exosomal miRNAs show promise as dual-function agents, modulating vascular homeostasis pathways while providing biomarker signatures for hypertension and its complications (37).

Exosomes exhibited distinct molecular signatures reflective of target organ injuries in hypertension. Ma et al. found that decreased miRNA-330-3p might contribute to cognitive impairment in hypertensive patients by decreasing frontal cerebrovascular reactivity, which could be a biomarker for early detection of cognitive impairment in hypertension (22). Since exosomes are first isolated and purified from urine (38), current study uncovers the diagnostic utility of urinary exosomes as dynamic indicators of renal metabolic status, offering noninvasive means to monitor both functional decline and structural damage in hypertensive kidney disease. Perez-Hernandez et al. found that miR-26a, a major regulator of TGF-β signaling, downregulated in urinary and plasma-derived exosomes of albuminuria in hypertension (23). Consistent with this finding, in vitro experiment showed a significant decrease in exosomal miR-26a levels in podocytes exposed to TGF-β1 (23). Complementing these findings, they subsequently identified exosomal miR-146a as a clinically relevant biomarker, showing an inverse correlation with albuminuria and discriminatory power for detecting urinary albumin excretion (12).

Exosomes derived from urine have been extensively investigated for their miRNAs. In 2013, Gildea et al. identified 45 miRNAs in urinary exosomes which were associated with salt-sensitive hypertension, of which 24 were, for the first time, discovered to be specific to urinary exosomes. These miRNAs modulate key signaling pathways implicated in hypertension, involving the metabolic activities of the kidney, especially the processing of sodium (39). Moreover, Zhang found that hypertensive patients with early renal damage exhibited notably decreased levels of miR-200a-3p and miR-29a-5p mRNA transcripts as compared to healthy individuals (29). In summary, urinary exosome miRNAs may serve as a promising biomarker to monitor sodium sensitivity of BP and identify early-stage renal injury in hypertension.

Beyond miRNA, urinary exosomes contain other biologically significant components that reflect renal pathophysiology. Researcher revealed that NCC expression in the urinary exosomes of patients with hypertension was significantly higher than that in controls in the Mongolian population (28). Research into Mendelian forms of hypertension has discovered alterations in the renal tubular sodium handling, particularly in distal convoluted tubule (DCT)-native, thiazide-sensitive NCC. Altered function of the NCC has profound effects on BP regulation (40). Another study reported that urinary exosome content could be regulated by renin-angiotensin-aldosterone system (RAAS) activation, and it was speculated that urinary measurement of exosomal γ-epithelial sodium channel (γENaC) concentration could be a useful biomarker of ENaC activation in clinical studies (41). Hypertension is associated with renal cellular injury. When cells are distressed, they release EVs, and the increased EVs in urine serve as an indicator of renal injury. Santelli et al. found that urinary p16⁺ EVs were elevated in patients with hypertension, potentially reflecting increased proximal tubular cellular senescence (24), which suggested that urinary EVs profiling could help identify intrarenal sites of cellular senescence.

Machine learning algorithms have ushered in a new paradigm for biomarker discovery in the post-genomic era. Reel et al. demonstrated this potential through their innovative application of computational methods to accurately classify hypertension subtypes using circulating miRNA profiles (42,43). Building on these advances and initial investigations of EV alterations across hypertension phenotypes (21), future research could employ machine learning to delineate distinct EV signatures across hypertension phenotypes, identify novel EV-associated biomarkers, and develop predictive models for clinical stratification.

Several limitations inherent in this systematic review should be considered: (I) potential regional bias: six studies were conducted in China, which might limit the generalizability of findings to other regions and populations; (II) insufficient reporting of key metrics: essential performance indicators (e.g., AUC, sensitivity/specificity, comorbidities) were frequently omitted; (III) clinical heterogeneity: critical data on hypertension severity/duration and antihypertensive medication were largely absent across studies; (IV) methodological variability in EV-RNA analysis: current methods varied widely in exosome extraction and analysis.

Future research priorities should focus on: (I) establishing standardized protocols for exosome research in hypertension studies research (44,45); (II) systematically comparing exosomal biomarkers against conventional markers; and (III) conducting large-scale, multi-ethnic prospective studies to validate race-specific signatures and longitudinal correlations with target organ damage. These comprehensive approaches may bridge the gap between basic research and clinical translation in hypertensive exosome studies.

Conclusions

This systematic review elucidated the value of blood and urine exosomal biomarkers in the early diagnosis, precise typing, and target organ damage monitoring of hypertension and its complications. To ensure the clinical relevance of exosomal biomarkers, future studies should directly compare them against conventional markers with standardized protocols. Such efforts should be coupled with strategies to enhance methodological rigor, including the acquisition of larger sample sizes, adherence to guidelines for complete and transparent reporting, and the creation of standardized repositories for data sharing.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the PRISMA reporting checklist. Available at https://cdt.amegroups.com/article/view/10.21037/cdt-2025-76/rc

Peer Review File: Available at https://cdt.amegroups.com/article/view/10.21037/cdt-2025-76/prf

Funding: This work was supported by the National Natural Science Foundation of China (Nos. 82104976, 82074516 and 82474618), the Sichuan Science and Technology Program (No. 2023JDRC0026), and the Xinglin Scholars Scientific Research Promotion Program of Chengdu University of Traditional Chinese Medicine (No. QJRC2022041).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://cdt.amegroups.com/article/view/10.21037/cdt-2025-76/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Olsen MH, Angell SY, Asma S, et al. A call to action and a lifecourse strategy to address the global burden of raised blood pressure on current and future generations: the Lancet Commission on hypertension. Lancet 2016;388:2665-712. [Crossref] [PubMed]
2. Zhou B, Perel P, Mensah GA, et al. Global epidemiology, health burden and effective interventions for elevated blood pressure and hypertension. Nat Rev Cardiol 2021;18:785-802. [Crossref] [PubMed]
3. NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants. Lancet 2021;398:957-80. [Crossref] [PubMed]
4. Carretero OA, Oparil S. Essential hypertension. Part I: definition and etiology. Circulation 2000;101:329-35. [Crossref] [PubMed]
5. Currie G, Delles C. Use of Biomarkers in the Evaluation and Treatment of Hypertensive Patients. Curr Hypertens Rep 2016;18:54. [Crossref] [PubMed]
6. Arif M, Sadayappan S, Becker RC, et al. Epigenetic modification: a regulatory mechanism in essential hypertension. Hypertens Res 2019;42:1099-113. [Crossref] [PubMed]
7. Mathivanan S, Fahner CJ, Reid GE, et al. ExoCarta 2012: database of exosomal proteins, RNA and lipids. Nucleic Acids Res 2012;40:D1241-4. [Crossref] [PubMed]
8. Valadi H, Ekström K, Bossios A, et al. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 2007;9:654-9. [Crossref] [PubMed]
9. Zhang Y, Liu Y, Liu H, et al. Exosomes: biogenesis, biologic function and clinical potential. Cell Biosci 2019;9:19. [Crossref] [PubMed]
10. Huda MN, Nafiujjaman M, Deaguero IG, et al. Potential Use of Exosomes as Diagnostic Biomarkers and in Targeted Drug Delivery: Progress in Clinical and Preclinical Applications. ACS Biomater Sci Eng 2021;7:2106-49. [Crossref] [PubMed]
11. Jayaseelan VP, Arumugam P. Exosomal microRNAs as a promising theragnostic tool for essential hypertension. Hypertens Res 2020;43:74-5. [Crossref] [PubMed]
12. Perez-Hernandez J, Olivares D, Forner MJ, et al. Urinary exosome miR-146a is a potential marker of albuminuria in essential hypertension. J Transl Med 2018;16:228. [Crossref] [PubMed]
13. Tan PPS, Hall D, Chilian WM, et al. Exosomal microRNAs in the development of essential hypertension and its potential as biomarkers. Am J Physiol Heart Circ Physiol 2021;320:H1486-97. [Crossref] [PubMed]
14. Pironti G, Strachan RT, Abraham D, et al. Circulating Exosomes Induced by Cardiac Pressure Overload Contain Functional Angiotensin II Type 1 Receptors. Circulation 2015;131:2120-30. [Crossref] [PubMed]
15. Rennenberg RJ, Kessels AG, Schurgers LJ, et al. Vascular calcifications as a marker of increased cardiovascular risk: a meta-analysis. Vasc Health Risk Manag 2009;5:185-97. [Crossref] [PubMed]
16. Furmanik M, van Gorp R, Whitehead M, et al. Endoplasmic Reticulum Stress Mediates Vascular Smooth Muscle Cell Calcification via Increased Release of Grp78 (Glucose-Regulated Protein, 78 kDa)-Loaded Extracellular Vesicles. Arterioscler Thromb Vasc Biol 2021;41:898-914. [Crossref] [PubMed]
17. Kondracki B, Kłoda M, Jusiak-Kłoda A, et al. MicroRNA Expression in Patients with Coronary Artery Disease and Hypertension-A Systematic Review. Int J Mol Sci 2024;25:6430. [Crossref] [PubMed]
18. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. Int J Surg 2021;88:105906. [Crossref] [PubMed]
19. Sterne JA, Hernán MA, Reeves BC, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ 2016;355:i4919. [Crossref] [PubMed]
20. Damkjaer M, Jensen PH, Schwämmle V, et al. Selective renal vasoconstriction, exaggerated natriuresis and excretion rates of exosomic proteins in essential hypertension. Acta Physiol (Oxf) 2014;212:106-18. [Crossref] [PubMed]
21. Lugo-Gavidia LM, Carnagarin R, Burger D, et al. Circulating platelet-derived extracellular vesicles correlate with night-time blood pressure and vascular organ damage and may represent an integrative biomarker of vascular health. J Clin Hypertens (Greenwich) 2022;24:738-49. [Crossref] [PubMed]
22. Ma J, Cao X, Chen F, et al. Exosomal MicroRNAs Contribute to Cognitive Impairment in Hypertensive Patients by Decreasing Frontal Cerebrovascular Reactivity. Front Neurosci 2021;15:614220. [Crossref] [PubMed]
23. Perez-Hernandez J, Riffo-Campos AL, Ortega A, et al. Urinary- and Plasma-Derived Exosomes Reveal a Distinct MicroRNA Signature Associated With Albuminuria in Hypertension. Hypertension 2021;77:960-71. [Crossref] [PubMed]
24. Santelli A, Sun IO, Eirin A, et al. Senescent Kidney Cells in Hypertensive Patients Release Urinary Extracellular Vesicles. J Am Heart Assoc 2019;8:e012584. [Crossref] [PubMed]
25. Wang C, Xing C, Li Z, et al. Bioinspired therapeutic platform based on extracellular vesicles for prevention of arterial wall remodeling in hypertension. Bioact Mater 2022;8:494-504. [Crossref] [PubMed]
26. Liu D. The clinical effect of Tai Chi on patients with essential hypertension and its influence on serum exosome microRNA expression levels. Chengdu University of Traditional Chinese Medicine; 2021.
27. Kong L. A Study on the Differential Expression of Plasma Exosomal miRNAs in Essential Hypertension Patients of Different Ethnic Groups in Xinjiang. Shihezi University; 2022.
28. Song H. The Relationship between Essential Hypertension and SLC12A3 Gene Polymorphism in Mongolian Population in Mongolian-majority Regions. Inner Mongolia Medical University; 2023.
29. Zhang J. Observation on the Therapeutic Effect of Yanggan Yishui Granules in Treating Early Renal Damage in Hypertension and the Influence of Exosomes. Anhui University of Chinese Medicine; 2024.
30. Nolde JM, Frost S, Kannenkeril D, et al. Capillary vascular density in the retina of hypertensive patients is associated with a non-dipping pattern independent of mean ambulatory blood pressure. J Hypertens 2021;39:1826-34. [Crossref] [PubMed]
31. Nolde JM, Kiuchi MG, Lugo-Gavidia LM, et al. Nocturnal hypertension: a common phenotype in a tertiary clinical setting associated with increased arterial stiffness and central blood pressure. J Hypertens 2021;39:250-8. [Crossref] [PubMed]
32. Mori MA, Ludwig RG, Garcia-Martin R, et al. Extracellular miRNAs: From Biomarkers to Mediators of Physiology and Disease. Cell Metab 2019;30:656-73. [Crossref] [PubMed]
33. Li H, Zhao J, Liu B, et al. MicroRNA-320 targeting neuropilin 1 inhibits proliferation and migration of vascular smooth muscle cells and neointimal formation. Int J Med Sci 2019;16:106-14. [Crossref] [PubMed]
34. Ling S, Nanhwan M, Qian J, et al. Modulation of microRNAs in hypertension-induced arterial remodeling through the β1 and β3-adrenoreceptor pathways. J Mol Cell Cardiol 2013;65:127-36. [Crossref] [PubMed]
35. Ren W, Liang L, Li Y, et al. Upregulation of miR 423 improves autologous vein graft restenosis via targeting ADAMTS 7. Int J Mol Med 2020;45:532-42. [Crossref] [PubMed]
36. Ren H, Guo Z, Liu Y, et al. Stem Cell-derived Exosomal MicroRNA as Therapy for Vascular Age-related Diseases. Aging Dis 2022;13:852-67. [Crossref] [PubMed]
37. Sudhakaran G, Arockiaraj J. The interplay of exosomal miRNAs in hypertension and aging. Hypertens Res 2024;47:3496-7. [Crossref] [PubMed]
38. Pisitkun T, Shen RF, Knepper MA. Identification and proteomic profiling of exosomes in human urine. Proc Natl Acad Sci U S A 2004;101:13368-73. [Crossref] [PubMed]
39. Gildea JJ, Carlson JM, Schoeffel CD, et al. Urinary exosome miRNome analysis and its applications to salt sensitivity of blood pressure. Clin Biochem 2013;46:1131-4. [Crossref] [PubMed]
40. Meor Azlan NF, Koeners MP, Zhang J. Regulatory control of the Na-Cl co-transporter NCC and its therapeutic potential for hypertension. Acta Pharm Sin B 2021;11:1117-28. [Crossref] [PubMed]
41. Qi Y, Wang X, Rose KL, et al. Activation of the Endogenous Renin-Angiotensin-Aldosterone System or Aldosterone Administration Increases Urinary Exosomal Sodium Channel Excretion. J Am Soc Nephrol 2016;27:646-56. [Crossref] [PubMed]
42. Reel PS, Reel S, Pearson E, et al. Using machine learning approaches for multi-omics data analysis: A review. Biotechnol Adv 2021;49:107739. [Crossref] [PubMed]
43. Reel S, Reel PS, Van Kralingen J, et al. Identification of hypertension subtypes using microRNA profiles and machine learning. Eur J Endocrinol 2025;192:418-28. [Crossref] [PubMed]
44. Welsh JA, Goberdhan DCI, O'Driscoll L, et al. Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches. J Extracell Vesicles 2024;13:e12404. [Crossref] [PubMed]
45. Miceli RT, Chen TY, Nose Y, et al. Extracellular vesicles, RNA sequencing, and bioinformatic analyses: Challenges, solutions, and recommendations. J Extracell Vesicles 2024;13:e70005. [Crossref] [PubMed]

(English Language Editor: J. Gray)