Whole blood and tissue miRNA expression profiles in children with congenital heart disease–associated pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a major complication of congenital heart disease (CHD) with left-to-right shunts. Early identification of pulmonary vascular alterations is critical for improving clinical outcomes. In this study, we aimed to determine circulating and tissue-associated miRNA expression profiles in children with CHD-associated PAH and to evaluate their association with disease severity. The expression profiles of 384 miRNAs were analyzed by real-time PCR in peripheral whole blood and pulmonary artery tissue samples obtained from children with CHD-associated PAH (n = 25) and healthy controls (n = 15). Blood samples were collected preoperatively and 10 days postoperatively. Pulmonary artery tissue samples were obtained during corrective surgery. Multiple circulating miRNAs were significantly dysregulated in PAH patients compared with controls. Among these, miR-200a-3p, miR-204-5p, and miR-184 showed the most prominent increases in preoperative blood samples. Distinct miRNA expression patterns were also observed according to pulmonary arterial pressure severity, with miR-499a-5p predominantly elevated in patients with PAP ≤ 40 mmHg and miR-656 increased in patients with PAP > 40 mmHg. Several circulating miRNAs demonstrated reduced expression in postoperative samples. In pulmonary artery tissue, miR-218, miR-146a-5p, and miR-144-3p were significantly increased in patients with more severe disease. Our findings demonstrate significant alterations in circulating and tissue-associated miRNA expression profiles in children with CHD-associated PAH. In particular, miR-200a-3p, miR-204-5p, and miR-184 emerged as potential candidate biomarkers associated with disease progression and pulmonary vascular remodeling. These findings support the potential role of miRNA dysregulation in the molecular pathogenesis of CHD-associated PAH.