Author + information
- Temo Barwari, MD,
- Abhishek Joshi, BA, BMBCh and
- Manuel Mayr, MD, PhD∗ ()
- ↵∗King’s British Heart Foundation Centre, King’s College London, 125 Coldharbour Lane, London SE5 9NU, United Kingdom
We appreciate the comments by Dr. Patanè on our review on microribonucleic acids (miRNAs) in cardiovascular disease. To concisely summarize the current knowledge and give our opinion on the way ahead, we have selected key publications that illustrate the great potential of this type of noncoding RNA. The vast number of studies that have been published in the past decade in this field require a balance between addressing the full breadth of cardiovascular disease, and a thorough critical appraisal of these fields.
With this in mind, we briefly touch on miRNA effects on cardiomyocyte apoptosis and regeneration. We highlight the study by Boon et al. (1), reporting a regulatory function of miR-34a on cardiomyocyte survival. These results build on previous studies with an oncological focus, reporting this miRNA to be induced by p53 and acting as a proapoptotic signal (2). On the other hand, miRNAs such as miR-590 and miR-199a were shown to promote cardiomyocyte proliferation through cell cycle re-entry (3). miR-199a has also been shown to reduce p53-mediated apoptosis in hypoxic cardiomyocytes (4). These studies illustrate the role that miRNAs seemingly play in apoptosis and proliferation, including the p53 pathway.
Steering cardiomyocytes toward regeneration can certainly be seen as a “Holy Grail” for heart failure therapy, and we applaud all efforts to further elucidate the mechanisms that are at play. On the other hand, there are profound differences in both miRNA expression and structural protein regulation between the (regenerative) zebrafish heart and the (proliferative) neonatal mouse heart compared with the adult mouse heart and human cardiomyocytes that lack these endogenous repair mechanisms (5). In our review, we aim to emphasize the systemic effects of miRNAs that come as a consequence of their expression across tissues and cell types. This is just as true for p53-related actions of miRNAs as it is for any others, on one hand protecting against dysplasia and on the other hand restricting repair of dysfunctional tissue in the failing heart. The lack of techniques that selectively target miRNAs in the heart remains a major impediment to clinical utility. Therefore, we argue for comprehensive evaluation of miRNA effects that takes into account their ubiquitous expression.
Please note: Dr. Mayr is a British Heart Foundation (BHF) Senior Research Fellow (FS/13/2/29892) and has been supported by the Fondation Leducq (MIRVAD; 13 CVD 02) and the National Institute for Health Research Biomedical Research Center based at Guy’s and St Thomas’ National Health Service Foundation Trust and King’s College London in partnership with King’s College Hospital; and is named an inventor on licensed patents for microRNA biomarkers. Dr. Barwari is an Interdisciplinary PhD student funded by the BHF. Dr. Joshi has been awarded a BHF Clinical Research Training Fellowship.
- 2017 American College of Cardiology Foundation
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