Serum and Tissue miRNA Expression Profiles of Pediatric Pulmonary Hypertensive Patients

Abstract Purpose: Pulmonary arterial hypertension is the major complication of the congenital heart diseases with left to right shunt. It is essential to diagnose these patients before developing pulmonary vascular disease. Scientists are in the search of a novel biomarker. In the present study we aimed to determine the miRNA expression profile in blood and heart tissue samples of children having pulmonary hypertension due to congenital heart disease. Method: The expression profiles of 384 miRNAs were determined in the blood and the heart tissue samples of the pulmonary hypertensive patients with Congenital heart defects (25 patients) in comparison with the healthy control group (15 patients) by real time PCR method. Tissue samples were taken from their pulmonary artery during surgery. Blood samples were repeated 10 days after surgery. Results: Twelve miRNAs miR-124-3p, miR-149-5p,miR-184,miR-200a-3p,miR-203a,miR-204-5p,miR-205-5p,miR-208b,miR-211-5p,miR-488-3p,miR-498,miR-885-5p) were found increased more than 100 times compared to the control. Among these miRNAs, miR-200a-3p, which increased 804 times preoperatively compared to the control group, draws attention. miR-499-5p levels were significantly high in patients with pulmonary arterial pressure<40mmHg. miR-656 was found significantly high in the patients whose PAP>40 mmHg. Expression of 10 miRNAs was decreased in postoperative period. In tissue samples 3 miRNAs (miR-218,miR-146-5p,miR-144-3p) were found significantly high in patients. Conclusion: Expression levels of miR-200a-3p, miR-204-5p, and miR-184 increased during the progression of PAH in the blood, and vanished after the surgery. This indicates that these 3miRNAs and their target genes and associated pathways can be used as a biomarker for the diagnosis or follow-up of the disease.