Michael A. Smith, Sam Chiacchia, Jason Boehme, Sanjeev A. Datar, Emily Morell, Roberta L. Keller, Amy Romer, Elizabeth Colglazier, Clair Parker, Jasmine Becerra, Jeffrey R. Fineman
University of California, San Francisco. Stanford University. Children’s Hospital of Philadelphia.
United States
American Journal of Physiology Heart and Circulatory Physiology
Am J Physiol Heart Circ Physiol 2024;
DOI: https://doi.org/10.1152/ajpheart.00622.2024
Abstract
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 pulmonary hypertension patients 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 pulmonary hypertension patients, 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 TGFβ beta, 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.
Category
Potential Biomarkers Associated with Pulmonary Vascular Disease
Diagnostic Testing for Pulmonary Vascular Disease. Non-invasive Testing
Diagnostic Testing for Pulmonary Vascular Disease. Invasive Testing
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
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