110 - MiRNA Expression associated with hemodynamically significant intracardiac shunt in low birth weight infants with bronchopulmonary dysplasia and pulmonary hypertension (BPD-PH)

Recent studies have highlighted the contribution of the developing pulmonary circulation to lung development, suggesting that premature infants with congenital cardiac defects are also at risk for pulmonary complications.  In addition, pulmonary over circulation leads to shear stress injury to the endothelium leading to an inflammatory response and eventual vascular remodeling and dysfunction. Disrupted vascularization and alveolarization during lung development contributes to the development of bronchopulmonary dysplasia (BPD and pulmonary hypertension (BPD-PH). Many genetic factors determine the pathogenesis of BPD and BPD-PH including miRNAs which are small RNAs that regulate gene expression.

Objective:

The purpose of this study was to elucidate miRNA expression associated with hemodynamically significant left to right shunt in low-birth-weight infants with BPD-PH.

Design/Methods:

infants. The demographics outlined below (Figure1). The inclusion criteria were very low birth weight (< 1500 g), echocardiogram performed at 36 weeks showing a PDA with a hemodynamically significant intracardiac shunt (ICS), and a diagnosis of BPD/ BPD-PH. Based on this criteria, 43 TA samples were analyzed (23 ICS-BPD-PH and 20 ICS-BPD). Small RNAs were extracted using the Norgen miRNA purification kit, and the expression of 1,066 human miRNAs was detected with PCR arrays (Qiagen). MiRNA expression was compared between ICS-BPD infants with and without PH using the Bioconductor limma package on R.  

Results:

The results of the study demonstrated 11 differentially expressed miRNAs between groups (adjusted p< 0.05) (Figure 2). Six miRNAs (hsa-mir-1468, 4330, 1287, 877, 216a, 200b) were downregulated and 5 were upregulated (hsa-mir-324-5p, 2116, 378b, 877, 150) in the infants with ICS-BPD-PH vs. those with ICS-BPD. An IPA Bioinformatic analysis of the differentially expressed miRNAs identified roles in cellular function including cellular growth, proliferation, death, survival, development, morphology and function. The top physiologic systems included: cardiovascular, hematological, humoral immunity, organismal development, and hair/skin development (Figure 3). 

Conclusion(s):

Eleven MiRNAs in TAs from infants with BPD and intracardiac shunts show differential expression in subjects with and without PH, an in-silico target prediction model identified VEGF, Insulin, VEGFA, STAT3, Hydrogen Peroxide as some of target molecules that could be playing a role in BPD-PH pathogenesis in low-birth-weight infants with ICS.