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Updated: Feb 19, 2026
In Vivo Nanovector Delivery of a Heart-specific MicroRNA-sponge
Published on: June 15, 2018
MicroRNAs regulating superoxide dismutase 2 are new circulating biomarkers of heart failure
Emilie Dubois-Deruy1, Marie Cuvelliez1, Jan Fiedler2
1INSERM, U1167, FHU-REMOD-HF, Institut Pasteur de Lille, University Lille Nord de France, 59800, Lille, France.
Abstract:
Although several risk factors such as infarct size have been identified, the progression of heart failure (HF) remains difficult to predict in clinical practice. Using an experimental rat model of post-myocardial infarction (MI), we previously identified 45 proteins differentially modulated during HF by proteomic analysis. This study sought to identify microRNAs (miRNAs) able to regulate these proteins and to test their relevance as biomarkers for HF. In silico bioinformatical analysis selected 13 miRNAs related to the 45 proteins previously identified. These miRNAs were analyzed in the rat and in cohorts of patients phenotyped for left ventricular remodeling (LVR). We identified that 3 miRNAs, miR-21-5p, miR-23a-3p and miR-222-3p, and their target Mn superoxide dismutase (SOD2) were significantly increased in LV and plasma of HF-rats. We found by luciferase activity a direct interaction of miR-222-3p with 3'UTR of SOD2. Transfection of human cardiomyocytes with miR-222-3p mimic or inhibitor induced respectively a decrease and an increase of SOD2 expression. Circulating levels of the 3 miRNAs and their target SOD2 were associated with high LVR post-MI in REVE-2 patients. We demonstrated for the first time the potential of microRNAs regulating SOD2 as new circulating biomarkers of HF.
Insights
Heart failure progression is hard to predict. This study identifies three microRNAs (miRNAs) and their target SOD2 as potential circulating biomarkers for heart failure, offering new diagnostic possibilities.
Area of Science:
- Biochemistry
- Molecular Biology
- Cardiology
Background:
- Heart failure (HF) progression is difficult to predict clinically.
- Previous proteomic analysis in a rat model identified 45 differentially modulated proteins during HF.
- Identifying regulatory microRNAs (miRNAs) for these proteins is crucial for biomarker discovery.
Purpose of the Study:
- To identify miRNAs regulating proteins associated with heart failure.
- To evaluate the potential of these miRNAs as circulating biomarkers for HF and left ventricular remodeling (LVR).
Main Methods:
- In silico bioinformatical analysis to select candidate miRNAs.
- Analysis of miRNA and target protein expression in rat models and human patient cohorts.
- Luciferase activity assays and cardiomyocyte transfection to confirm miRNA-target interaction.
Main Results:
- Three specific miRNAs (miR-21-5p, miR-23a-3p, miR-222-3p) and their target Mn superoxide dismutase (SOD2) were elevated in HF rats.
- Direct interaction between miR-222-3p and SOD2 was confirmed.
- Circulating levels of these miRNAs and SOD2 correlated with LVR in post-myocardial infarction patients.
Conclusions:
- MicroRNAs regulating SOD2 show potential as novel circulating biomarkers for heart failure.
- This finding offers new avenues for predicting HF progression and LVR.
- The study establishes a link between specific miRNAs, SOD2, and HF pathophysiology.
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