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The let-7b-5p, miR-326, and miR-125a-3p are associated with left ventricular systolic dysfunction in post-myocardial
Raquel Costa Silva Dantas-Komatsu1, Marina Sampaio Cruz1,2, Paula Paccielli Freire1,3
1Postgraduate Program in Health Sciences, Federal University of Rio Grande do Norte, Natal, Brazil.
Insights
Specific microRNAs, including let-7b-5p, miR-125a-3p, and miR-326, are altered in patients with left ventricular systolic dysfunction (LVSd) after myocardial infarction. These microRNAs may serve as potential biomarkers for predicting LVSd development post-STEMI.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Epigenetics
Background:
- Acute ST-elevation myocardial infarction (STEMI) can cause adverse cardiac remodeling, leading to left ventricular systolic dysfunction (LVSd) and heart failure.
- MicroRNAs (miRNAs), as epigenetic regulators, are implicated in the pathophysiology of LVSd.
Purpose of the Study:
- To explore the role of specific microRNAs in peripheral blood mononuclear cells (PBMC) of patients who experienced myocardial infarction and developed LVSd.
- To identify potential miRNA biomarkers for LVSd post-STEMI.
Main Methods:
- Analysis of 61 microRNAs in PBMCs from post-STEMI patients with (n=9) and without (n=16) LVSd using RT-qPCR.
- Identification of differentially expressed miRNAs, followed by Principal Component Analysis and logistic regression for LVSd prediction.
- System biology approach and enrichment analysis to explore miRNA-target regulatory networks and associated biological pathways.
Main Results:
- let-7b-5p, miR-125a-3p, and miR-326 were significantly upregulated in LVSd patients compared to non-LVSd controls.
- These three miRNAs effectively discriminated between LVSd and non-LVSd groups (AUC > 0.78).
- let-7b-5p and miR-326 were identified as independent predictors of LVSd (p < 0.05).
- Enrichment analysis indicated that the targets of these miRNAs are involved in immunological response, cell-cell adhesion, and cardiac remodeling.
Conclusions:
- Left ventricular systolic dysfunction (LVSd) post-STEMI is associated with altered expression of let-7b-5p, miR-326, and miR-125a-3p in PBMCs.
- These miRNAs show potential as diagnostic and predictive biomarkers for LVSd following myocardial infarction.
- The findings suggest a role for these miRNAs in the physiopathology of cardiac dysfunction after STEMI.
Background:
Acute ST-elevation myocardial infarction (STEMI) can lead to adverse cardiac remodeling, resulting in left ventricular systolic dysfunction (LVSd) and heart failure. Epigenetic regulators, such as microRNAs, may be involved in the physiopathology of LVSd.
Objective:
This study explored microRNAs in peripheral blood mononuclear cells (PBMC) of post-myocardial infarction patients with LVSd.
Methods:
Post-STEMI patients were grouped as having (LVSd, n = 9) or not LVSd (non-LVSd, n = 16). The expression of 61 microRNAs was analyzed in PBMC by RT-qPCR and the differentially expressed microRNAs were identified. Principal Component Analysis stratified the microRNAs based on the development of dysfunction. Predictive variables of LVSd were investigated through logistic regression analysis. A system biology approach was used to explore the regulatory molecular network of the disease and an enrichment analysis was performed.
Results:
The let-7b-5p (AUC: 0.807; 95% CI: 0.63-0.98; p = 0.013), miR-125a-3p (AUC: 0.800; 95% CI: 0.61-0.99; p = 0.036) and miR-326 (AUC: 0.783; 95% CI: 0.54-1.00; p = 0.028) were upregulated in LVSd (p < 0.05) and discriminated LVSd from non-LVSd. Multivariate logistic regression analysis showed let-7b-5p (OR: 16.00; 95% CI: 1.54-166.05; p = 0.020) and miR-326 (OR: 28.00; 95% CI: 2.42-323.70; p = 0.008) as predictors of LVSd. The enrichment analysis revealed association of the targets of these three microRNAs with immunological response, cell-cell adhesion, and cardiac changes.
Conclusion:
LVSd alters the expression of let-7b-5p, miR-326, and miR-125a-3p in PBMC from post-STEMI, indicating their potential involvement in the cardiac dysfunction physiopathology and highlighting these miRNAs as possible LVSd biomarkers.
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