Early Salivary and Tracheal aspirate miRNAs in Extremely Preterm Infants Predict BPD-related Pulmonary Hypertension

ABSTRACT: Pulmonary hypertension (BPD-PH) associated with bronchopulmonary dysplasia (BPD) in preterm infants is associated with high morbidity and mortality within the first two years of life. In a previous unbiased study, we identified a panel 16 miRNAs in tracheal aspirates (TA) that were differentially expressed in preterm infants with BPD-PH compared to those with BPD but no PH. To endotype molecular thumbprint of BPD-PH, we used unbiased multiomics approach and identified a panel of miRNAs, mRNAs, and proteins in tracheal aspirates (TA) and found 14 differentially expressed mIRNAs. To explore to predictive potential of these miRNAs, we collected TA and extracted exosomes from extremely low gestational age infants (ELGANs) at 7 days of age and calculated the predictive AUROC of these miRNAs from TA exosomes to diagnose BPD-PH at 36 weeks PMA. AUROC of TA miRNAs was 0.89 with sensitivity and specificity of 77% and 81%, respectively. Due to challenges of obtaining TA in non-invasively ventilated infants, we collected saliva samples (SA) from ELGANs at 7 days of age and calculated the predictive AUROC of the same miRNAs to diagnose BPD-PH at 36 weeks PMA. AUROC of these miRNAs in saliva was = 0.94 with sensitivity and specificity of 93% and 78%, respectively. Of the 14 miRNAs, of particular interest is miR29-a which is highly differentially expressed in BPD-PH and has been studied in animal model for its role in modulating genes responsible for lung growth and development. We studied the effect of miR29-a on the pulmonary artery smooth muscle cells (PASMC) by transfecting them with Ago-miR29a and found low expression PDGFA which is an important key player in angiogenesis and lung development in early growth. Salivary miRNA panel is a potential non-invasive early predictor of BPD-PH in ELGANs with biological plausibility through miR29a pathway.

ORGANISM(S): Homo sapiens

PROVIDER: GSE326620 | GEO | 2026/08/01

REPOSITORIES: GEO