Multi‐microRNA diagnostic panel for heart failure with preserved ejection fraction in preclinical and clinical settings

Abstract Aims Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome accounting for half of heart failure cases. Although natriuretic peptides are the most accepted and extensively used biomarkers for heart failure, their diagnostic accuracy for HFpEF remains debatable. Here, w...

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Main Authors: Reza Parvan, Natale Rolim, Andreas B. Gevaert, Alessandro Cataliotti, Emeline M. vanCraenenbroeck, Volker Adams, Ulrik Wisløff, Gustavo Jose Justo Silva, the OptimEx Study Group
Format: Article
Language:English
Published: Wiley 2025-08-01
Series:ESC Heart Failure
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Online Access:https://doi.org/10.1002/ehf2.15324
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author Reza Parvan
Natale Rolim
Andreas B. Gevaert
Alessandro Cataliotti
Emeline M. vanCraenenbroeck
Volker Adams
Ulrik Wisløff
Gustavo Jose Justo Silva
the OptimEx Study Group
author_facet Reza Parvan
Natale Rolim
Andreas B. Gevaert
Alessandro Cataliotti
Emeline M. vanCraenenbroeck
Volker Adams
Ulrik Wisløff
Gustavo Jose Justo Silva
the OptimEx Study Group
author_sort Reza Parvan
collection DOAJ
description Abstract Aims Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome accounting for half of heart failure cases. Although natriuretic peptides are the most accepted and extensively used biomarkers for heart failure, their diagnostic accuracy for HFpEF remains debatable. Here, we aimed to identify a panel of circulating microRNAs (miRNAs) as potential novel biomarkers for diagnosis of HFpEF in a preclinical model, subsequently validated in human HFpEF patients. Methods and results In a female hypertension‐induced HFpEF model [Dahl/Salt Sensitive (DSS) rats], circulating miRNA levels were screened in the plasma via real‐time quantitative polymerase chain reaction. DSS rats exhibited HFpEF features as indicated by diastolic dysfunction and adverse cardiac remodelling when fed a high‐salt (8%) diet (n = 11) compared with a low‐salt (0.3%) diet (n = 15). A panel of four circulating miRNAs (rno‐let‐7b‐5p, rno‐let‐7e‐5p, rno‐miR‐21‐5p and rno‐miR‐140‐3p) were found significantly altered in the DSS plasma. Clinical performance of miRNA expression analysis was assessed in publicly available datasets of human heart failure patients, including assessment of discrimination of different categories of heart failure [GSE53437; control = 30, heart failure with reduced ejection fraction (HFrEF) = 41, HFpEF = 19] and gender differences (GSE104150; female = 6, male = 10). The miRNA panel significantly discriminated HFpEF patients from healthy individuals and HFrEF patients. We also found significant downregulation of let‐7b‐5p and miR‐21‐5p in females compared with males, regardless of health status. Conclusions A panel of four circulating miRNAs was differently expressed in female HFpEF rats and significantly discriminated HFpEF patients from healthy individuals and HFrEF patients. This cross‐species and bench‐to‐bedside approach demonstrates the potential of miRNA‐based panels for HFpEF diagnosis.
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spelling doaj-art-ffc1cce385ca4da9b8e0eeea2cdb4ec22025-08-20T02:50:51ZengWileyESC Heart Failure2055-58222025-08-011243028304110.1002/ehf2.15324Multi‐microRNA diagnostic panel for heart failure with preserved ejection fraction in preclinical and clinical settingsReza Parvan0Natale Rolim1Andreas B. Gevaert2Alessandro Cataliotti3Emeline M. vanCraenenbroeck4Volker Adams5Ulrik Wisløff6Gustavo Jose Justo Silva7the OptimEx Study GroupInstitute for Experimental Medical Research Oslo University Hospital and University of Oslo Oslo NorwayDepartment of Circulation and Medical Imaging Norwegian University of Science and Technology Trondheim NorwayResearch Group Cardiovascular Diseases, GENCOR Department University of Antwerp Antwerp BelgiumInstitute for Experimental Medical Research Oslo University Hospital and University of Oslo Oslo NorwayResearch Group Cardiovascular Diseases, GENCOR Department University of Antwerp Antwerp BelgiumLaboratory of Molecular and Experimental Cardiology TU Dresden, Heart Center Dresden Dresden GermanyDepartment of Circulation and Medical Imaging Norwegian University of Science and Technology Trondheim NorwayDepartment of Molecular Medicine, Institute of Basic Medical Sciences University of Oslo Oslo NorwayAbstract Aims Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome accounting for half of heart failure cases. Although natriuretic peptides are the most accepted and extensively used biomarkers for heart failure, their diagnostic accuracy for HFpEF remains debatable. Here, we aimed to identify a panel of circulating microRNAs (miRNAs) as potential novel biomarkers for diagnosis of HFpEF in a preclinical model, subsequently validated in human HFpEF patients. Methods and results In a female hypertension‐induced HFpEF model [Dahl/Salt Sensitive (DSS) rats], circulating miRNA levels were screened in the plasma via real‐time quantitative polymerase chain reaction. DSS rats exhibited HFpEF features as indicated by diastolic dysfunction and adverse cardiac remodelling when fed a high‐salt (8%) diet (n = 11) compared with a low‐salt (0.3%) diet (n = 15). A panel of four circulating miRNAs (rno‐let‐7b‐5p, rno‐let‐7e‐5p, rno‐miR‐21‐5p and rno‐miR‐140‐3p) were found significantly altered in the DSS plasma. Clinical performance of miRNA expression analysis was assessed in publicly available datasets of human heart failure patients, including assessment of discrimination of different categories of heart failure [GSE53437; control = 30, heart failure with reduced ejection fraction (HFrEF) = 41, HFpEF = 19] and gender differences (GSE104150; female = 6, male = 10). The miRNA panel significantly discriminated HFpEF patients from healthy individuals and HFrEF patients. We also found significant downregulation of let‐7b‐5p and miR‐21‐5p in females compared with males, regardless of health status. Conclusions A panel of four circulating miRNAs was differently expressed in female HFpEF rats and significantly discriminated HFpEF patients from healthy individuals and HFrEF patients. This cross‐species and bench‐to‐bedside approach demonstrates the potential of miRNA‐based panels for HFpEF diagnosis.https://doi.org/10.1002/ehf2.15324cross‐species validationdiagnosisHFpEFHFrEFmicroRNA
spellingShingle Reza Parvan
Natale Rolim
Andreas B. Gevaert
Alessandro Cataliotti
Emeline M. vanCraenenbroeck
Volker Adams
Ulrik Wisløff
Gustavo Jose Justo Silva
the OptimEx Study Group
Multi‐microRNA diagnostic panel for heart failure with preserved ejection fraction in preclinical and clinical settings
ESC Heart Failure
cross‐species validation
diagnosis
HFpEF
HFrEF
microRNA
title Multi‐microRNA diagnostic panel for heart failure with preserved ejection fraction in preclinical and clinical settings
title_full Multi‐microRNA diagnostic panel for heart failure with preserved ejection fraction in preclinical and clinical settings
title_fullStr Multi‐microRNA diagnostic panel for heart failure with preserved ejection fraction in preclinical and clinical settings
title_full_unstemmed Multi‐microRNA diagnostic panel for heart failure with preserved ejection fraction in preclinical and clinical settings
title_short Multi‐microRNA diagnostic panel for heart failure with preserved ejection fraction in preclinical and clinical settings
title_sort multi microrna diagnostic panel for heart failure with preserved ejection fraction in preclinical and clinical settings
topic cross‐species validation
diagnosis
HFpEF
HFrEF
microRNA
url https://doi.org/10.1002/ehf2.15324
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