Circulating microRNA as a Novel Biomarker for Pulmonary Arterial Hypertension Due to Congenital Heart Disease

Circulating microRNAs (miRNAs) have recently been indicated as practical and promising biomarkers for various diseases. However, circulating miRNAs have not been found to be biomarkers for pulmonary arterial hypertension (PAH) due to congenital heart disease. PAH is defined by a mean pulmonary arterial pressure (mPAP) >25 mmHg at rest. Blood samples and lung tissues were collected from patients with severe PAH due to ventricular septal defect (VSD) (PAH group, mPAP >45 mmHg, n=14) and patients with VSD but non-PAH (control group, mPAP <25 mmHg, n=16). Total RNA was extracted from the tissues and the plasma collected, and the different expression of miRNAs in tissues was detected by miRNA arrays. Selected miRNAs were also verified using real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Levels of miR-19a were quantified in the plasma of 30 patients. We also conducted receiver–operator characteristic curve analysis to evaluate the diagnostic ability of miR-19a; 78 microRNAs changed more than twofold. The changes in miR-19a, miR-130a, and miR-27b were also confirmed using qRT-PCR. miR-19a was then analyzed in prospectively collected plasma taken from both groups. The levels of miR-19a were significantly increased in the PAH samples. The value of the area under the receiver-operating characteristic curve was 0.781 (95% confidence interval, CI = 0.612–0.950, P < 0.0001) for the miR-19a assay. Circulating miR-19a turned out to be a pronounced marker for PAH. Our observations suggest that miR-19a expression is enhanced in PAH blood. Circulating miR-19a may be a novel biomarker for the diagnosis of PAH.