Shelley D Miyamoto1, Anis Karimpour-Fard2, Valencia Peterson3, Scott R Auerbach4, Kurt R Stenmark5, Brian L Stauffer6, Carmen C Sucharov3. 1. Department of Pediatrics, University of Colorado School of Medicine, Children's Hospital Colorado, Aurora, Colorado. Electronic address: shelley.miyamoto@childrenscolorado.org. 2. Departments of Pharmacology and Medicine. 3. Division of Cardiology. 4. Department of Pediatrics, University of Colorado School of Medicine, Children's Hospital Colorado, Aurora, Colorado. 5. Cardiovascular Pulmonary Research Laboratory, University of Colorado, Denver, Colorado. 6. Division of Cardiology; Division of Cardiology, Denver Health and Hospital Authority, Denver, Colorado.
Abstract
BACKGROUND: MicroRNAs (miRNAs) are short regulatory RNAs that control gene expression through interacting with the 3'UTR of target messenger RNAs. The purpose of this study was to determine if circulating miRNAs are useful biomarkers of outcome in children with dilated cardiomyopathy (DCM). METHODS: An array for 754 miRNAs and real time polymerase chain reaction confirmation of select miRNAs were performed. Serum from 55 children <18 years old with DCM was analyzed. Samples were drawn from all patients with DCM when undergoing heart transplant evaluation and/or at the time of transplantation. Patients with DCM were categorized based on when their blood was drawn (Pre-Transplant or Transplant) and outcome (Transplant/died or Recovered). RESULTS: Two miRNAs were significantly up-regulated (hsa-miR-155 and hsa-miR-636) and 2 miRNAs were down-regulated (hsa-miR-646 and hsa-miR-639) in patients with DCM who were transplanted or died compared with patients with DCM who recovered their ventricular function. Receiver operator curves, performed for differences in any 1 of these 4 differentially regulated miRNAs in patients who were transplanted or died compared with patients who recovered, resulted in an area under the receiver operating characteristic curve of 0.875 for the Pre-Transplant blood draw time point and an area under the receiver operating characteristic curve of 0.93 for the day of Transplant time point. CONCLUSIONS: We identified specific miRNAs that are differentially regulated between children with DCM who need a transplant compared with children with DCM who recover. A unique biomarker signature of miRNAs that are specific to children with DCM who have the potential to recover would be valuable in risk stratification of this challenging patient population.
BACKGROUND: MicroRNAs (miRNAs) are short regulatory RNAs that control gene expression through interacting with the 3'UTR of target messenger RNAs. The purpose of this study was to determine if circulating miRNAs are useful biomarkers of outcome in children with dilated cardiomyopathy (DCM). METHODS: An array for 754 miRNAs and real time polymerase chain reaction confirmation of select miRNAs were performed. Serum from 55 children <18 years old with DCM was analyzed. Samples were drawn from all patients with DCM when undergoing heart transplant evaluation and/or at the time of transplantation. Patients with DCM were categorized based on when their blood was drawn (Pre-Transplant or Transplant) and outcome (Transplant/died or Recovered). RESULTS: Two miRNAs were significantly up-regulated (hsa-miR-155 and hsa-miR-636) and 2 miRNAs were down-regulated (hsa-miR-646 and hsa-miR-639) in patients with DCM who were transplanted or died compared with patients with DCM who recovered their ventricular function. Receiver operator curves, performed for differences in any 1 of these 4 differentially regulated miRNAs in patients who were transplanted or died compared with patients who recovered, resulted in an area under the receiver operating characteristic curve of 0.875 for the Pre-Transplant blood draw time point and an area under the receiver operating characteristic curve of 0.93 for the day of Transplant time point. CONCLUSIONS: We identified specific miRNAs that are differentially regulated between children with DCM who need a transplant compared with children with DCM who recover. A unique biomarker signature of miRNAs that are specific to children with DCM who have the potential to recover would be valuable in risk stratification of this challenging patient population.
Authors: Teresa M Lee; Daphne T Hsu; Paul Kantor; Jeffrey A Towbin; Stephanie M Ware; Steven D Colan; Wendy K Chung; John L Jefferies; Joseph W Rossano; Chesney D Castleberry; Linda J Addonizio; Ashwin K Lal; Jacqueline M Lamour; Erin M Miller; Philip T Thrush; Jason D Czachor; Hiedy Razoky; Ashley Hill; Steven E Lipshultz Journal: Circ Res Date: 2017-09-15 Impact factor: 17.367
Authors: Carmen C Sucharov; David P Kao; J David Port; Anis Karimpour-Fard; Robert A Quaife; Wayne Minobe; Karin Nunley; Brian D Lowes; Edward M Gilbert; Michael R Bristow Journal: JCI Insight Date: 2017-01-26
Authors: Rocío Toro; Sara Blasco-Turrión; Francisco José Morales-Ponce; Pablo Gonzalez; Pablo Martínez-Camblor; Amador López-Granados; Ramon Brugada; Oscar Campuzano; Alexandra Pérez-Serra; Felix Rosa Longobardo; Alipio Mangas; Vicenta Llorente-Cortes; David de Gonzalo-Calvo Journal: J Mol Med (Berl) Date: 2018-07-14 Impact factor: 4.599