title: Circulating microRNAs for predicting and monitoring response to mechanical circulatory support from a left ventricular assist device.
abstract: OBJECTIVE
  There are few non-invasive techniques to predict and monitor patients' responses to left ventricular assist device (LVAD) therapy. MicroRNAs (miRs) are small non-coding RNAs with intricate roles in cardiovascular disease. They are stable in the circulation, readily quantified, and may be useful as new biomarkers. This study sought to identify candidate miR biomarkers for further investigation.
  
  
  RESULTS
  We studied 53 plasma and 20 myocardial samples from 19 patients who underwent HeartMate II LVAD implantation, and used a screening microarray to analyse the change in expression of 1113 miRs after 6 months LVAD support. Twelve miRs showed significant variation and underwent validation, yielding miR-1202 and miR-483-3p as candidate biomarkers. In the test cohort, circulating miR-483-3p showed early and sustained up-regulation with LVAD support, with median (interquartile range) fold changes from baseline of 2.17 (1.43-2.62; P = 0.011), 2.27 (1.12-2.42; P = 0.036), 1.87 (1.64-4.36; P = 0.028), and 2.82 (0.70-10.62; P = 0.249) at 3, 6, 9, and 12 months, respectively, whilst baseline plasma miR-1202 identified good vs. poor LVAD responders [absolute expression 1.296 (1.293-1.306) vs. 1.311 (1.310-1.318) arbitrary units; P = 0.004]. Both miRs are enriched in ventricular myocardium, suggesting the heart as the possible source of the plasma fraction.
  
  
  CONCLUSIONS
  This is the first report of circulating miR biomarkers in LVAD patients. We demonstrate the feasibility of this approach, report the potential for miR-483-3p and miR-1202, respectively, to monitor and predict response to LVAD therapy, and propose further work to study these hypotheses and elucidate roles for miR-483-3p and miR-1202 in clinical practice and in underlying biological processes.
authors: National Institute for Health Research Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust, London, UK; National Heart and Lung Institute, Imperial College London, London, UK; Institute of Molecular and Translational Therapeutic Strategies, Integrated Research and Treatment Center Transplantation, Hannover Medical School, Hannover, Germany.
authors: Andrew C
authors: AC
authors: Morley-Smith
authors: Adam
authors: A
authors: Mills
authors: Steven
authors: S
authors: Jacobs
authors: Bart
authors: B
authors: Meyns
authors: Filip
authors: F
authors: Rega
authors: André R
authors: AR
authors: Simon
authors: John R
authors: JR
authors: Pepper
authors: Alexander R
authors: AR
authors: Lyon
authors: Thomas
authors: T
authors: Thum
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D006333:Heart Failure / Q000378:metabolism* / Q000628:therapy; D006353:Heart-Assist Devices; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D035683:MicroRNAs
keywords: Biomarker; MicroRNA; Ventricular assist device