A differential signature of down-regulated miRNAs in the plasma of chronic heart failure patients was identified, with specific combinations discriminating between HFpEF and HFrEF.
Case-Control
Does miRNA profiling identify differential signatures and pathways in patients with chronic heart failure compared to a reference group?
A specific signature of down-regulated miRNAs in plasma can discriminate between HFpEF and HFrEF, and ischaemic versus non-ischaemic aetiology, highlighting novel cellular mechanisms in chronic heart failure.
Heart failure (HF) is a complex disease entity with high clinical impact, poorly understood pathophysiology and scantly known miRNA-mediated epigenetic regulation. We have analysed miRNA patterns in patients with chronic HF (cHF) and a sex- and age-matched reference group and pursued an in silico system biology analysis to discern pathways involved in cHF pathophysiology. Twenty-eight miRNAs were identified in cHF that were up-regulated in the reference group, and eight of them were validated by RT-qPCR. In silico analysis of predicted targets by STRING protein-protein interaction networks revealed eight cluster networks (involving seven of the identified miRNAs) enriched in pathways related to cell cycle, Ras, chemokine, PI3K-AKT and TGF-β signaling. By ROC curve analysis, combined probabilities of these seven miRNAs (let-7a-5p, miR-107, miR-125a-5p, miR-139-5p, miR-150-5p, miR-30b-5p and miR-342-3p; clusters 1–4 C:1–4), discriminated between HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF), and ischaemic and non-ischaemic aetiology. A combination of miR-107, miR-139-5p and miR-150-5p, involved in clusters 5 and 7 (C:5+7), discriminated HFpEF from HFrEF. Pathway enrichment analysis of miRNAs present in C:1–4 (let-7a-5p, miR-125a-5p, miR-30b-5p and miR-342-3p) revealed pathways related to HF pathogenesis. In conclusion, we have identified a differential signature of down-regulated miRNAs in the plasma of HF patients and propose novel cellular mechanisms involved in cHF pathogenesis.
Vilella-Figuerola et al. (Sat,) conducted a case-control in Chronic Heart Failure. miRNA pattern analysis vs. Sex- and age-matched reference group was evaluated on Identification of miRNA patterns and pathways involved in cHF pathophysiology. A differential signature of down-regulated miRNAs in the plasma of chronic heart failure patients was identified, with specific combinations discriminating between HFpEF and HFrEF.