Identification of circulating microRNA biomarkers in pulmonary hypertension of group 2 for early detection

Pulmonary hypertension (PH) is a progressive cardiopulmonary disorder with high morbidity and mortality, yet non-invasive diagnostic biomarkers remain scarce. Circulating microRNAs (miRNAs) have emerged as promising biomarkers for various diseases, but their role in Group 2 PH (due to left heart disease) is poorly understood.

We performed high-throughput miRNA sequencing on plasma samples from 10 healthy controls (C group), 10 patients with coronary heart disease (CHD group), and 10 patients with coronary heart disease complicated by PH (PH group). Differential miRNA expression was analyzed, and candidate miRNAs were validated by RT-qPCR. Correlations with pulmonary artery pressure parameters (Tricuspid regurgitation maximum velocity (TRVmax) and systolic pulmonary artery pressure (SPAP) were assessed, and bioinformatic analyses were conducted to predict target genes and functional pathways.

We identified 575 differentially expressed miRNAs across the three groups. Eleven miRNAs were significantly dysregulated in PH patients compared to CHD and C groups. Among these, five miRNAs (mmu-miR-452-3p_1ss20GA, hsa-miR-10a-3p_R-1, hsa-miR-21-5p, hsa-miR-1287-5p_R + 1, and bta-mir-1246-p5_1ss18AG) showed strong positive correlations with TRVmax and SPAP. Receiver operating characteristic (ROC) curve analyses revealed high diagnostic accuracy. Functional enrichment analysis indicated involvement in key signaling pathways such as p53, PPAR, TGF-β, JAK-STAT, and MAPK.

Our study identifies a panel of circulating miRNAs as potential non-invasive biomarkers for diagnosing Group 2 PH and provides insights into their roles in PH pathogenesis, offering new avenues for therapeutic intervention.