Circulating microRNAs for predicting and monitoring response to mechanical circulatory support from a left
Andrew C Morley-Smith1, Adam Mills, Steven Jacobs
1National 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.
Aims:
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.
Methods And 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.
