Circulating microRNAs as potential candidate biomarkers of left ventricular reverse remodeling after myocardial infarction: A pilot study

BACKGROUND: Myocardial infarction (MI) induces cardiac remodeling and lead to heart failure. Some patients experience reverse remodeling, characterized by improved LV function. MicroRNAs (miRNAs) regulate gene expression and play a crucial role in remodeling processes. OBJECTIVES: We aimed to investigate the role of miRNAs in cardiac reverse remodeling after MI and identify candidate miRNAs that could predict better response to cardiac rehabilitation. METHODS: The study enrolled 39 patients following their first MI. For final analysis, 10 patients meeting echocardiographic criteria for LVRR at 8-week follow-up (absolute LVEF increase ≥ 10% or LVESV reduction ≥ 15%) were matched with 10 patients with stable LV status (SLVS). All patients completed a cardiac rehabilitation program. Expression of 375 circulating miRNAs was quantified - those with higher baseline accumulation in the LVRR group were identified as candidate biomarkers and their target genes were analyzed. RESULTS: Twenty patients (mean age 57 ± 9 years) were analyzed. At baseline, the SLVS group exhibited significantly higher LVEF compared to the LVRR group (53% vs. 44%, p = 0.013). Baseline regional contractility impairment in all LVRR patients was reversed in 70% of them at follow-up. Fourteen miRNAs (-15b-5p, -24-3p, -29c-3p, -99b-5p, -127-3p, -146a-5p, -199a-3p, -361-5p, -502-5p, -625-5p, -376c-3p, -18b-5p, -342-5p, and -429) were identified as candidate LVRR biomarkers. Enrichment analysis linked their targets to PI3K-Akt, MAPK, FoxO, and HIF-1 pathways. CONCLUSIONS: This study identifies 14 candidate miRNAs as LVRR biomarkers post-MI. These findings highlight the biological relevance of non-coding RNA and support the need for further research and validation in large, non-pooled cohorts. UNSTRUCTURED ABSTRACT: Myocardial infarction triggers adverse cardiac remodeling, though some patients achieve left ventricular reverse remodeling (LVRR), marked by functional and structural recovery. This pilot study investigated 39 patients to identify circulating microRNAs (miRNAs) that predict positive responses to cardiac rehabilitation. Comparing 10 LVRR responders against 10 stable patients, we quantified 375 miRNAs via RT-qPCR. At baseline, the stable group had higher ejection fractions (53% vs. 44%, p = 0.013), but 70% of LVRR patients reversed regional contractility impairment by the 8-week follow-up. We identified 14 potential biomarkers, including novel candidates (miR-502-5p, miR-376c-3p, and miR-18b-5p), whose target genes enrich pathways like PI3K-Akt, MAPK, and FoxO. These findings bridge the gap between preclinical data and clinical settings, highlighting the therapeutic potential of non-coding RNAs in cardiac reverse remodeling and necessitating further validation in larger cohorts.