| Autor: |
Smith MA; Division of Pediatric Critical Care, Department of Pediatrics, University of California, San Francisco, California, United States.; Division of Pediatric Pulmonary Hypertension, Department of Pediatrics, University of California, San Francisco, California, United States., Chiacchia S; Department of Emergency Medicine, Stanford University, Palo Alto, California, United States., Boehme J; Division of Pediatric Critical Care, Department of Pediatrics, University of California, San Francisco, California, United States., Datar SA; Division of Pediatric Critical Care, Department of Pediatrics, University of California, San Francisco, California, United States., Morell E; Division of Pediatric Critical Care, Department of Pediatrics, University of California, San Francisco, California, United States., Keller RL; Division of Pediatric Pulmonary Hypertension, Department of Pediatrics, University of California, San Francisco, California, United States.; Division of Neonatology, Department of Pediatrics, University of California, San Francisco, California, United States., Romer A; Division of Pediatric Critical Care, Department of Pediatrics, Children's Hospital of Philadelphia, Pennsylvania, United States., Colglazier E; Division of Pediatric Pulmonary Hypertension, Department of Pediatrics, University of California, San Francisco, California, United States., Parker C; Division of Pediatric Pulmonary Hypertension, Department of Pediatrics, University of California, San Francisco, California, United States., Becerra J; Division of Pediatric Pulmonary Hypertension, Department of Pediatrics, University of California, San Francisco, California, United States., Fineman JR; Division of Pediatric Critical Care, Department of Pediatrics, University of California, San Francisco, California, United States.; Division of Pediatric Pulmonary Hypertension, Department of Pediatrics, University of California, San Francisco, California, United States. |
| Abstrakt: |
Pediatric pulmonary hypertension is a heterogeneous disease associated with significant morbidity and mortality. MicroRNAs have been implicated as both pathologic drivers of disease and potential therapeutic targets in pediatric pulmonary hypertension. We sought to characterize the circulating microRNA profiles of a diverse array of pediatric patients with pulmonary hypertension using high-throughput sequencing technology. Peripheral blood samples were drawn from patients recruited at the time of a clinically indicated cardiac catheterization, and microRNA sequencing followed by differential expression and target/pathway enrichment analyses were performed. Among 63 pediatric patients with pulmonary hypertension, we identified specific microRNA signatures that uniquely classified patients by disease subtype, correlated with indicators of disease severity including invasive hemodynamic metrics, and changed over the course of treatment for pulmonary hypertension. These microRNA profiles include a number of specific microRNA molecules known to function in signaling pathways critical to pulmonary vascular biology and disease, including transforming growth factor-β (TGF-β), VEGF, PI3K/Akt, cGMP-PKG, and HIF-1 signaling. Circulating levels of miR-122-5p, miR-124-3p, miR-204-5p, and miR-9-5p decreased over the course of treatment in a subset of patients who had multiple samples drawn during the study period. Our findings support the further investigation of specific microRNAs as mechanistic mediators, biomarkers, and therapeutic targets in pulmonary hypertension. NEW & NOTEWORTHY We present novel insight into the circulating microRNA profiles of pediatric patients with pulmonary hypertension. Our findings support the utility of microRNAs as both useful biomarkers of disease severity and potential therapeutic targets in pediatric pulmonary hypertension. |
