Emery Lucy, Hughes Alexa, Oji-Mmuo Christiana, Silveyra Patricia, Aluquin Vincent P R, Donnelly Ann, Siddaiah Roopa
Penn State Health College of Medicine, Hershey, PA, USA.
Department of Pediatrics, Penn State Health Children's Hospital, Hershey, PA, USA.
Pediatr Res. 2024 Sep 13. doi: 10.1038/s41390-024-03541-5.
PDA and ASD are common intracardiac shunts noted in prematurely born infants. While there is evidence of persistent PDA and ASD associated with a higher risk for developing bronchopulmonary dysplasia (ICS-BPD) and pulmonary hypertension (ICS-BPD-PH), the underlying pathogenesis is poorly understood and hence challenging to identify at-risk infants. Our study goal was to evaluate transcriptomic expression and associated pathways in tracheal aspirates (TAs) of low-birth-weight infants with hemodynamically significant cardiac shunt (ICS) that develop bronchopulmonary dysplasia (ICS-BPD) and pulmonary hypertension (ICS-BPD-PH).
TAs were collected from preterm infants with ICS and a diagnosis of BPD or BPD-PH from a single center. 36 TA samples including 19 ICS-BPD and 17 ICS-BPD-PH were analyzed. MiRNA expression was determined via PCR arrays, and mRNA expression via RNA seq. Data were analyzed using limma.
11 miRNAs and 10 mRNAs were differentially expressed (adjusted p < 0.05) in ICS-BPD-PH group when compared to ICS-BPD. Ingenuity Pathway Analysis identified associations with cellular growth, proliferation, death, and cell function pathways.
TAs from preterm infants show differentially expressed miRNAs and mRNAs in ICS-BPD-PH when compared to ICS-BPD, an in-silico model identified target molecules that could be playing a role in BPD-PH pathogenesis in low-birth-weight infants with ICS.
Pulmonary hypertension associated with severe BPD (BPD-PH) is a distinct disease in preterm infants with severe BPD and the role of intracardiac shunt (ICS) in its development is controversial and often challenging for clinical management. Our pilot study, researching specific endotyping of infants with pulmonary hypertension associated with BPD using multiomics approach has identified molecular markers and potential underlying pathways associated with this condition. These markers could aid in stratifying high risk infants with ICS that are at risk for developing BPD-PH and aid clinical management.
动脉导管未闭（PDA）和房间隔缺损（ASD）是早产儿常见的心内分流。虽然有证据表明持续性PDA和ASD与发生支气管肺发育不良（ICS-BPD）和肺动脉高压（ICS-BPD-PH）的较高风险相关，但潜在的发病机制尚不清楚，因此难以识别高危婴儿。我们的研究目标是评估患有血流动力学显著心脏分流（ICS）并发生支气管肺发育不良（ICS-BPD）和肺动脉高压（ICS-BPD-PH）的低体重婴儿气管吸出物（TA）中的转录组表达及相关通路。
从单一中心收集患有ICS且诊断为BPD或BPD-PH的早产儿的TA。分析了36份TA样本，包括19份ICS-BPD样本和17份ICS-BPD-PH样本。通过PCR阵列测定miRNA表达，通过RNA测序测定mRNA表达。使用limma分析数据。
与ICS-BPD组相比，ICS-BPD-PH组中有11种miRNA和10种mRNA差异表达（校正p<0.05）。 Ingenuity通路分析确定了与细胞生长、增殖、死亡和细胞功能通路的关联。
与ICS-BPD相比，早产儿的TA在ICS-BPD-PH中显示出差异表达的miRNA和mRNA，一个计算机模型确定了可能在患有ICS的低体重婴儿BPD-PH发病机制中起作用的靶分子。
与重度BPD相关的肺动脉高压（BPD-PH）在患有重度BPD的早产儿中是一种独特的疾病，心内分流（ICS）在其发展中的作用存在争议，且对临床管理常常具有挑战性。我们的初步研究使用多组学方法研究与BPD相关的肺动脉高压婴儿的特定内型，已经确定了与这种情况相关的分子标记和潜在的基础通路。这些标记物有助于对有发展为BPD-PH风险的患有ICS的高危婴儿进行分层，并有助于临床管理。
