MicroRNA Profiling of Plasma Exosomes in Heart Failure Characterized by Reduced Ejection Fraction Reveals hsa-miR-339-5p as a Regulator of Ventricular Remodeling via NOD-like Receptor Family CARD Domain-Containing 5
Background: Heart failure characterized by reduced ejection fraction (HFrEF) is characterized by impaired cardiac function, with myocardial remodeling being a key pathological change in its progression. Plasma exosomal microRNAs(miRNAs) are promising non-invasive biomarkers with potential applications in the early prevention and treatment of HFrEF. Materials and methods: We used high-throughput miRNA sequencing to analyze plasma exosomes from 5 patients with heart failure with reduced ejection fraction (HFrEF) and 5 healthy volunteers to identify differentially expressed miRNAs. The miRanda program, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and WikiPathways were used for target gene prediction and pathway analysis. Using quantitative reverse transcription polymerase chain reaction (qRT-PCR), the expression of exosomal miRNAs was verified in plasma samples from 40 patients with HFrEF and 40 healthy controls. Differential ventricular remodeling miRNAs and target genes predicted by miRanda were verified by qRT-PCR (n=40). Results: In comparison to healthy controls, high-throughput sequencing of the plasma exosomes of HFrEF patients showed that 10 miRNAs were significantly upregulated and 17 miRNAs were significantly downregulated. qRT-PCR validation confirmed that hsa-miR-22-5p, hsa-miR-181b-5p, and hsa-miR-339-5p were significantly upregulated (P < 0.05), while hsa-miR-192-5p (P < 0.05) and hsa-miR-1469 (P < 0.01) were significantly downregulated. No significant difference was observed for hsa-miR-320a-3p (P > 0.05). According to bioinformatics studies, hsa-miR-339-5p regulates the PI3K/AKT signaling pathway to target NOD-like receptor family CARD domain-containing 5 (NLRC5), impacting myocardial remodeling. The plasma levels of NLRC5 were lower in the HFrEF group than in the control group (P<0.01), whereas the mRNA levels of PI3K and AKT were higher in the HFrEF group than in the control group (P<0.01). Conclusion: This study highlights the distinct manifestation of plasma exosomal miRNAs in HFrEF and confirms the function of hsa-miR-339-5p in promoting ventricular remodeling through NLRC5. Potential as a treatment target for HFrEF has been demonstrated by hsa-miR-339-5p, providing new directions for future treatment strategies. Overall design: high-throughput miRNA sequencing to analyze plasma exosomes from 5 patients with heart failure with reduced ejection fraction (HFrEF) and 5 healthy volunteers to identify differentially expressed miRNAs. The miRanda program, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and WikiPathways were used for target gene prediction and pathway analysis. Using quantitative reverse transcription polymerase chain reaction (qRT-PCR), the expression of exosomal miRNAs was verified in plasma samples from 40 patients with HFrEF and 40 healthy controls. Differential ventricular remodeling miRNAs and target genes predicted by miRanda were verified by qRT-PCR (n=40).