Logo: to the web site of Uppsala University

uu.sePublications from Uppsala University
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Serum microRNAs as peripheral markers of primary aldosteronism
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.ORCID iD: 0009-0002-7866-677X
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.ORCID iD: 0000-0003-3748-3176
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.ORCID iD: 0000-0002-9625-1394
Show others and affiliations
2025 (English)In: Frontiers in Endocrinology, E-ISSN 1664-2392Article in journal (Refereed) Published
Abstract [en]

Background: Primary aldosteronism (PA) is the principal cause of secondaryhypertension; it leads to significantly elevated cardiovascular morbidity andmortality, but only a fraction of its cases ever get detected, partially due todiagnostic procedures that are difficult to perform and to interpret. Morestraightforward diagnostic methods are needed. Lateralized, or unilateral PA(uPA), is best treated by surgery. Bilateral PA (bPA) is treated medically.Aim: The aim of our study was to explore microRNA (miRNA) in peripheral bloodas markers of PA, uPA and bPA.

Methods: In groups of subjects with primary hypertension (HT, n = 11), bPA (n =12), and uPA (n = 16), peripheral serum was used for isolation of total RNA, librarypreparation, and NGS sequencing to achieve a comparative analysis of miRNAexpression. Five-fold cross-validation support vector machine learning (ML)models were employed to search for miRNA that could be used as markers ofPA and its forms.

Results: In our cohort of patients, the discovered combinations of miRNAs could,with a high level of accuracy, sensitivity, and specificity, characterize thedifference between HT and PA, as well as between a combined group of HT +bPA vs. uPA. The differentiating parameters were moderately good forcomparison of bPA vs. uPA.

Conclusion: Within our patient cohort, and using ML, the study identifieddistinctly different miRNA profiles between HT and PA, as well as between bPAand uPA. Further validation studies may lead to the emergence of a new tool forclinical diagnostics of PA.

Place, publisher, year, edition, pages
Lausanne: Frontiers Media S.A., 2025.
National Category
Surgery
Research subject
Medical Science
Identifiers
URN: urn:nbn:se:uu:diva-553580DOI: 10.3389/fendo.2025.1511096ISI: 001457813300001PubMedID: 40182638Scopus ID: 2-s2.0-105001691132OAI: oai:DiVA.org:uu-553580DiVA, id: diva2:1948400
Available from: 2025-03-28 Created: 2025-03-28 Last updated: 2025-04-24Bibliographically approved
In thesis
1. Primary aldosteronism: improving screening-based diagnostics and treatment
Open this publication in new window or tab >>Primary aldosteronism: improving screening-based diagnostics and treatment
2025 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Primary aldosteronism (PA, non-physiologic adrenal overproduction of aldosterone) causes about 10% of arterial hypertension, and substantially elevates morbidity and cardiovascular mortality compared to primary hypertension (HT) alone.  PA often lacks specific clinical traits, and remains mostly undiagnosed. Its diagnosis requires biochemical screening and confirmatory tests - which are quite difficult to perform and/or to interpret correctly. About a quarter of PA cases are lateralized (or unilateral, uPA) – and can be cured or significantly ameliorated by surgery, which gives the best long-term prognosis. Bilateral subtype (bPA) can be controlled by mineralocorticoid receptor antagonists. Even the current lateralizing procedures are technically demand-ing and invasive. The challenge of identifying PA and its subtypes to guide the treatment requires more straightforward and sensitive diagnostic methods.

Our first paper describes the project of screening of 1181 unselected primary care hypertensive patients for PA. The 53 found cases of PA (corresponding to a prevalence of 4,5%) were further evaluated and treated (surgically or medically) according to the current guidelines. The pathophysiologic and clinical aspects of the recommended diagnostic and treatment principles, and the follow-up results after at least 6 months after treatment initiation were presented and analyzed.

Our second and third papers present research of new peripheral blood markers that may support diagnostics of PA among hypertensive individuals, including differentiation between its lateralized and bilateral subtype. MicroRNAs (second paper) and proteomic profile (third paper) were analyzed in groups of well clinically studied patients with HT, bPA and uPA.

MicroRNAs have been shown to regulate both aldosterone production and its effects in the target-tissues. Using machine learning (ML), we demonstrate the potential of both microRNAs (analyzed by NGS) and proteomics (analyzed by Olink® Explore 384 Cardiometabolic Panel based on proximity extension assay) to differentiate PA from HT, and uPA from bPA. Further validating studies are needed to evaluate the constructed ML-models and the clinical utility of both microRNA and proteomic analysis in hypertensive patients.

The theoretic and practical experience of these studies confirms the necessity to actively screen hypertensive patients for PA and to further develop its diagnostic methods as specific treatment ameliorates the long-term prognosis. 

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2025. p. 47
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 2159
Keywords
primary aldosteronism, diagnostics, treatment, surgery, screening, primary care, biomarkers, microRNA, proteomics, prevalence
National Category
Surgery
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-554431 (URN)978-91-513-2501-9 (ISBN)
Public defence
2025-06-12, H:son Holmdahlsalen, Akademiska sjukhuset, ingång 100, Uppsala, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2025-05-21 Created: 2025-04-24 Last updated: 2025-05-21

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMedScopus

Authority records

Makhnov, NikitaAxling, FredrikBarazeghi, ElhamStålberg, PeterÅkerström, TobiasHellman, Per

Search in DiVA

By author/editor
Makhnov, NikitaAxling, FredrikBarazeghi, ElhamStålberg, PeterÅkerström, TobiasHellman, Per
By organisation
Endocrine SurgeryDepartment of Surgical SciencesExperimental Surgery
In the same journal
Frontiers in Endocrinology
Surgery

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 50 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf